Re: [ccp4bb] All-D World
I believe Eric is paraphrasing Genesis 3. It's all the serpent's fault. http://www.ic.unicamp.br/~stolfi/PUB/misc-misc/GenesysParody.html http://www.ic.unicamp.br/%7Estolfi/PUB/misc-misc/GenesysParody.html On 16/02/2012 02:39, Eric Bennett wrote: Jacob, I wish it were that cheery. Do not forget the darker side of history. The prefix L- stands for levorotary. The levo comes from the Latin wording for left side. Left handedness is also known as sinistrality, from the Latin sinistra which also meant the left side, but over time took on the connotations that we currently associate with the word sinister. The latter word, of course, is generally associated with dark and evil. It is therefore erroneous to attribute the L amino acid to the Almighty. The L amino acid is in fact a diabolical corruption of cellular processes that begin with the D-nucleotide (D- meaning rotating to the right, but derived from dexter, meaning dextrous and skillful). The instrument which causes this perversion of God's perfect righteousness into a sign of evil deserves our strongest moral condemnation... I am referring, of course, to that devilish piece of cellular machinery known as the ribosome. The discovery of the ribosome was a significant blow to the success of what Charles Baudelaire famously called the devil's greatest trick. For years now, his acolytes have attempted to hide the truth about the ribosome by referring to its work with the neutral, innocent-sounding phrase translation. Don't be fooled, but instead pray for the development of the next generation of ribosome inhibitors, or at least dissolve the current generation in holy water before ingesting. -Eric On Feb 15, 2012, at 7:24 PM, Jacob Keller wrote: G-d is right-handed, so to speak: Ex 15:6 Thy right hand, O LORD, is become glorious in power: thy right hand, O LORD, hath dashed in pieces the enemy. Since we are made in His image, and our (chiral) molecules are the cause of making most of us right-handed, which enantiomer to use was not a real choice but rather flowed logically from His (right-handed) Essence. Our chirality is dictated by His, whatever that means! JPK On Wed, Feb 15, 2012 at 4:48 PM, William G. Scottwgsc...@ucsc.edu wrote: Hi Jacob: After giving this a great deal of reflection ….. I realized that you would face the same paradox that God had to resolve six thousand years ago at the Dawn of Creation, i.e., He needed D-deoxyribose DNA to code for L-amino acid proteins, and vice versa. Likewise, you would probably be faced with a situation where you need L-deoxyribose DNA to code for D-amino acid proteins, so once again, you need a ribozyme self-replicase to escape the Irreducible Complexity(™). (The Central Dogma at least is achiral.) At least it can be done six thousand years, which isn't unreasonable for a Ph.D. thesis project (especially when combined with an M.D.), and you, unlike Him, have access to a Sigma catalogue. All the best, Bill William G. Scott Professor Department of Chemistry and Biochemistry and The Center for the Molecular Biology of RNA 228 Sinsheimer Laboratories University of California at Santa Cruz Santa Cruz, California 95064 USA On Feb 15, 2012, at 10:28 AM, Jacob Keller wrote: So who out there wants to start an all-D microbial culture by total synthesis, a la the bacterium with the synthetic genome a while back? Could it work, I wonder? I guess that would be a certain benchmark for Man's conquest of nature. JPK ps maybe if there is a broadly-acting amino-acid isomerase or set of isomerases of appropriate properties, this could be helpful for getting the culture started--or even for preying on the L world? On Wed, Feb 15, 2012 at 12:17 PM, David Schullerdj...@cornell.edu wrote: On 02/15/12 12:41, Jacob Keller wrote: Are there any all-D proteins out there, of known structure or otherwise? If so, do enantiomer-specific catalyses become inverted? JPK What do you mean by Out There? If you mean in the PDB, then yes. As of two weeks ago, there are ~ 14 racemic structures deposited; most in space group P -1, with one outlier in space group I -4 C 2. This includes RNA, DNA, and PNA, but 6 entries are actually protein. The longest is over 80 residues. Theoretically, enantiomer-specific catalysis ought to be inverted, but most of the structures solved are not enzymes. kaliotoxin, plectasin, antifreeze protein, monellin, villin, and a designed peptide. On the other hand, if by out there you meant in nature outside of biochemistry and organic chemistry labs; then no, I am not aware of any all-D proteins. There are a few protein/peptides which include a small number of D-residues, which is marked up to nonribosomal synthesis. The first paper I managed to Google: http://jb.asm.org/content/185/24/7036.full Learning from Nature's Drug Factories: Nonribosomal Synthesis of Macrocyclic Peptides doi: 10.1128/JB.185.24.7036-7043.2003 J. Bacteriol. December 2003 vol. 185 no.
[ccp4bb] All-D World
So who out there wants to start an all-D microbial culture by total synthesis, a la the bacterium with the synthetic genome a while back? Could it work, I wonder? I guess that would be a certain benchmark for Man's conquest of nature. JPK ps maybe if there is a broadly-acting amino-acid isomerase or set of isomerases of appropriate properties, this could be helpful for getting the culture started--or even for preying on the L world? On Wed, Feb 15, 2012 at 12:17 PM, David Schuller dj...@cornell.edu wrote: On 02/15/12 12:41, Jacob Keller wrote: Are there any all-D proteins out there, of known structure or otherwise? If so, do enantiomer-specific catalyses become inverted? JPK What do you mean by Out There? If you mean in the PDB, then yes. As of two weeks ago, there are ~ 14 racemic structures deposited; most in space group P -1, with one outlier in space group I -4 C 2. This includes RNA, DNA, and PNA, but 6 entries are actually protein. The longest is over 80 residues. Theoretically, enantiomer-specific catalysis ought to be inverted, but most of the structures solved are not enzymes. kaliotoxin, plectasin, antifreeze protein, monellin, villin, and a designed peptide. On the other hand, if by out there you meant in nature outside of biochemistry and organic chemistry labs; then no, I am not aware of any all-D proteins. There are a few protein/peptides which include a small number of D-residues, which is marked up to nonribosomal synthesis. The first paper I managed to Google: http://jb.asm.org/content/185/24/7036.full Learning from Nature's Drug Factories: Nonribosomal Synthesis of Macrocyclic Peptides doi: 10.1128/JB.185.24.7036-7043.2003 J. Bacteriol. December 2003 vol. 185 no. 24 7036-7043 If racemic crystallization isn't exciting enough for you, look into quasi-racemic crystallization. On Wed, Feb 15, 2012 at 8:05 AM, David Schuller dj...@cornell.edu wrote: Wukovitz Yeates (1995) Nature Struc. Biol. 2(12): 1062-1067 predicts that the most probable space group for macromolecular crystallization is P -1 (P 1-bar). All you have to do to try it out is synthesize the all-D enantiomer of your protein and get it to fold properly. On 02/14/12 18:36, Prem Kaushal wrote: Hi We have a protein that crystallized in P21212 space group. We are looking for some different crystal forms. We tried few things did not work. Now we are thinking to mutate surface residues. Anybody aware of any software which can predict the mutations that might help in crystallizing protein in different space group, please inform me. Thanks in advance Prem -- === All Things Serve the Beam === David J. Schuller modern man in a post-modern world MacCHESS, Cornell University schul...@cornell.edu -- *** Jacob Pearson Keller Northwestern University Medical Scientist Training Program email: j-kell...@northwestern.edu ***
Re: [ccp4bb] All-D World
The structure of an all D-amino acid version of the HIV-1 protease was solved in 1992 (see Milton, Milton, and Kent, 1992, Science, 256:1445-1448). The D-enzyme was seen to have a structure that is the mirror image of the L-enzyme, and showed specificity for the enantiomeric form of the chiral substrate. P. Shing Ho, PhD Professor Chair Department of Biochemistry Molecular Biology Colorado State University Fort Collins, CO 80524-1870 On 2/15/12 11:28 AM, Jacob Keller j-kell...@fsm.northwestern.edu wrote: So who out there wants to start an all-D microbial culture by total synthesis, a la the bacterium with the synthetic genome a while back? Could it work, I wonder? I guess that would be a certain benchmark for Man's conquest of nature. JPK ps maybe if there is a broadly-acting amino-acid isomerase or set of isomerases of appropriate properties, this could be helpful for getting the culture started--or even for preying on the L world? On Wed, Feb 15, 2012 at 12:17 PM, David Schuller dj...@cornell.edu wrote: On 02/15/12 12:41, Jacob Keller wrote: Are there any all-D proteins out there, of known structure or otherwise? If so, do enantiomer-specific catalyses become inverted? JPK What do you mean by Out There? If you mean in the PDB, then yes. As of two weeks ago, there are ~ 14 racemic structures deposited; most in space group P -1, with one outlier in space group I -4 C 2. This includes RNA, DNA, and PNA, but 6 entries are actually protein. The longest is over 80 residues. Theoretically, enantiomer-specific catalysis ought to be inverted, but most of the structures solved are not enzymes. kaliotoxin, plectasin, antifreeze protein, monellin, villin, and a designed peptide. On the other hand, if by out there you meant in nature outside of biochemistry and organic chemistry labs; then no, I am not aware of any all-D proteins. There are a few protein/peptides which include a small number of D-residues, which is marked up to nonribosomal synthesis. The first paper I managed to Google: http://jb.asm.org/content/185/24/7036.full Learning from Nature's Drug Factories: Nonribosomal Synthesis of Macrocyclic Peptides doi: 10.1128/JB.185.24.7036-7043.2003 J. Bacteriol. December 2003 vol. 185 no. 24 7036-7043 If racemic crystallization isn't exciting enough for you, look into quasi-racemic crystallization. On Wed, Feb 15, 2012 at 8:05 AM, David Schuller dj...@cornell.edu wrote: Wukovitz Yeates (1995) Nature Struc. Biol. 2(12): 1062-1067 predicts that the most probable space group for macromolecular crystallization is P -1 (P 1-bar). All you have to do to try it out is synthesize the all-D enantiomer of your protein and get it to fold properly. On 02/14/12 18:36, Prem Kaushal wrote: Hi We have a protein that crystallized in P21212 space group. We are looking for some different crystal forms. We tried few things did not work. Now we are thinking to mutate surface residues. Anybody aware of any software which can predict the mutations that might help in crystallizing protein in different space group, please inform me. Thanks in advance Prem -- === All Things Serve the Beam === David J. Schuller modern man in a post-modern world MacCHESS, Cornell University schul...@cornell.edu -- *** Jacob Pearson Keller Northwestern University Medical Scientist Training Program email: j-kell...@northwestern.edu ***
[ccp4bb] ccp4bb] All-D World
Weds., Feb. 15th 2012 EBI Good evening, PDB entries with spg P 1- or I -4 C 2 are 3al1 3boi 2gpm 1krl 2gq7 2gq6 2gq5 2gq4 2g32 1pup 3e7r 1vtu 3odv 3trw 3try you can get information on each from pdbe pdbe.org/entry i.e. pdbe.org/3al1 etc. Miri, PDBe On Wed, 15 Feb 2012, Jacob Keller wrote: So who out there wants to start an all-D microbial culture by total synthesis, a la the bacterium with the synthetic genome a while back? Could it work, I wonder? I guess that would be a certain benchmark for Man's conquest of nature. JPK ps maybe if there is a broadly-acting amino-acid isomerase or set of isomerases of appropriate properties, this could be helpful for getting the culture started--or even for preying on the L world? On Wed, Feb 15, 2012 at 12:17 PM, David Schuller dj...@cornell.edu wrote: On 02/15/12 12:41, Jacob Keller wrote: Are there any all-D proteins out there, of known structure or otherwise? If so, do enantiomer-specific catalyses become inverted? JPK What do you mean by Out There? If you mean in the PDB, then yes. As of two weeks ago, there are ~ 14 racemic structures deposited; most in space group P -1, with one outlier in space group I -4 C 2. This includes RNA, DNA, and PNA, but 6 entries are actually protein. The longest is over 80 residues. Theoretically, enantiomer-specific catalysis ought to be inverted, but most of the structures solved are not enzymes. kaliotoxin, plectasin, antifreeze protein, monellin, villin, and a designed peptide. On the other hand, if by out there you meant in nature outside of biochemistry and organic chemistry labs; then no, I am not aware of any all-D proteins. There are a few protein/peptides which include a small number of D-residues, which is marked up to nonribosomal synthesis. The first paper I managed to Google: http://jb.asm.org/content/185/24/7036.full Learning from Nature's Drug Factories: Nonribosomal Synthesis of Macrocyclic Peptides doi: 10.1128/JB.185.24.7036-7043.2003 J. Bacteriol. December 2003 vol. 185 no. 24 7036-7043 If racemic crystallization isn't exciting enough for you, look into quasi-racemic crystallization. On Wed, Feb 15, 2012 at 8:05 AM, David Schuller dj...@cornell.edu wrote: Wukovitz Yeates (1995) Nature Struc. Biol. 2(12): 1062-1067 predicts that the most probable space group for macromolecular crystallization is P -1 (P 1-bar). All you have to do to try it out is synthesize the all-D enantiomer of your protein and get it to fold properly. On 02/14/12 18:36, Prem Kaushal wrote: Hi We have a protein that crystallized in P21212 space group. We are looking for some different crystal forms. We tried few things did not work. Now we are thinking to mutate surface residues. Anybody aware of any software which can predict the mutations that might help in crystallizing protein in different space group, please inform me. Thanks in advance Prem -- === All Things Serve the Beam === David J. Schuller modern man in a post-modern world MacCHESS, Cornell University schul...@cornell.edu -- *** Jacob Pearson Keller Northwestern University Medical Scientist Training Program email: j-kell...@northwestern.edu *** Weds. Feb. 15th, 2012 EBI
Re: [ccp4bb] All-D World
Hi Jacob: After giving this a great deal of reflection ….. I realized that you would face the same paradox that God had to resolve six thousand years ago at the Dawn of Creation, i.e., He needed D-deoxyribose DNA to code for L-amino acid proteins, and vice versa. Likewise, you would probably be faced with a situation where you need L-deoxyribose DNA to code for D-amino acid proteins, so once again, you need a ribozyme self-replicase to escape the Irreducible Complexity(™). (The Central Dogma at least is achiral.) At least it can be done six thousand years, which isn't unreasonable for a Ph.D. thesis project (especially when combined with an M.D.), and you, unlike Him, have access to a Sigma catalogue. All the best, Bill William G. Scott Professor Department of Chemistry and Biochemistry and The Center for the Molecular Biology of RNA 228 Sinsheimer Laboratories University of California at Santa Cruz Santa Cruz, California 95064 USA On Feb 15, 2012, at 10:28 AM, Jacob Keller wrote: So who out there wants to start an all-D microbial culture by total synthesis, a la the bacterium with the synthetic genome a while back? Could it work, I wonder? I guess that would be a certain benchmark for Man's conquest of nature. JPK ps maybe if there is a broadly-acting amino-acid isomerase or set of isomerases of appropriate properties, this could be helpful for getting the culture started--or even for preying on the L world? On Wed, Feb 15, 2012 at 12:17 PM, David Schuller dj...@cornell.edu wrote: On 02/15/12 12:41, Jacob Keller wrote: Are there any all-D proteins out there, of known structure or otherwise? If so, do enantiomer-specific catalyses become inverted? JPK What do you mean by Out There? If you mean in the PDB, then yes. As of two weeks ago, there are ~ 14 racemic structures deposited; most in space group P -1, with one outlier in space group I -4 C 2. This includes RNA, DNA, and PNA, but 6 entries are actually protein. The longest is over 80 residues. Theoretically, enantiomer-specific catalysis ought to be inverted, but most of the structures solved are not enzymes. kaliotoxin, plectasin, antifreeze protein, monellin, villin, and a designed peptide. On the other hand, if by out there you meant in nature outside of biochemistry and organic chemistry labs; then no, I am not aware of any all-D proteins. There are a few protein/peptides which include a small number of D-residues, which is marked up to nonribosomal synthesis. The first paper I managed to Google: http://jb.asm.org/content/185/24/7036.full Learning from Nature's Drug Factories: Nonribosomal Synthesis of Macrocyclic Peptides doi: 10.1128/JB.185.24.7036-7043.2003 J. Bacteriol. December 2003 vol. 185 no. 24 7036-7043 If racemic crystallization isn't exciting enough for you, look into quasi-racemic crystallization. On Wed, Feb 15, 2012 at 8:05 AM, David Schuller dj...@cornell.edu wrote: Wukovitz Yeates (1995) Nature Struc. Biol. 2(12): 1062-1067 predicts that the most probable space group for macromolecular crystallization is P -1 (P 1-bar). All you have to do to try it out is synthesize the all-D enantiomer of your protein and get it to fold properly. On 02/14/12 18:36, Prem Kaushal wrote: Hi We have a protein that crystallized in P21212 space group. We are looking for some different crystal forms. We tried few things did not work. Now we are thinking to mutate surface residues. Anybody aware of any software which can predict the mutations that might help in crystallizing protein in different space group, please inform me. Thanks in advance Prem -- === All Things Serve the Beam === David J. Schuller modern man in a post-modern world MacCHESS, Cornell University schul...@cornell.edu -- *** Jacob Pearson Keller Northwestern University Medical Scientist Training Program email: j-kell...@northwestern.edu ***
Re: [ccp4bb] All-D World
Well if you think about it technically God produced plants within three days which if far too little work for a thesis. Maybe it could count as preliminary results for one aim of a thesis proposal so it might be enough to get PhD candidacy depending on how demanding your committee is. You could always propose the remaining 5999 years and 362 days to do a massive data mining initiative. Thanks for the laugh. I needed it. Katherine On Wed, Feb 15, 2012 at 4:48 PM, William G. Scott wgsc...@ucsc.edu wrote: Hi Jacob: After giving this a great deal of reflection ….. I realized that you would face the same paradox that God had to resolve six thousand years ago at the Dawn of Creation, i.e., He needed D-deoxyribose DNA to code for L-amino acid proteins, and vice versa. Likewise, you would probably be faced with a situation where you need L-deoxyribose DNA to code for D-amino acid proteins, so once again, you need a ribozyme self-replicase to escape the Irreducible Complexity(™). (The Central Dogma at least is achiral.) At least it can be done six thousand years, which isn't unreasonable for a Ph.D. thesis project (especially when combined with an M.D.), and you, unlike Him, have access to a Sigma catalogue. All the best, Bill William G. Scott Professor Department of Chemistry and Biochemistry and The Center for the Molecular Biology of RNA 228 Sinsheimer Laboratories University of California at Santa Cruz Santa Cruz, California 95064 USA On Feb 15, 2012, at 10:28 AM, Jacob Keller wrote: So who out there wants to start an all-D microbial culture by total synthesis, a la the bacterium with the synthetic genome a while back? Could it work, I wonder? I guess that would be a certain benchmark for Man's conquest of nature. JPK ps maybe if there is a broadly-acting amino-acid isomerase or set of isomerases of appropriate properties, this could be helpful for getting the culture started--or even for preying on the L world? On Wed, Feb 15, 2012 at 12:17 PM, David Schuller dj...@cornell.edu wrote: On 02/15/12 12:41, Jacob Keller wrote: Are there any all-D proteins out there, of known structure or otherwise? If so, do enantiomer-specific catalyses become inverted? JPK What do you mean by Out There? If you mean in the PDB, then yes. As of two weeks ago, there are ~ 14 racemic structures deposited; most in space group P -1, with one outlier in space group I -4 C 2. This includes RNA, DNA, and PNA, but 6 entries are actually protein. The longest is over 80 residues. Theoretically, enantiomer-specific catalysis ought to be inverted, but most of the structures solved are not enzymes. kaliotoxin, plectasin, antifreeze protein, monellin, villin, and a designed peptide. On the other hand, if by out there you meant in nature outside of biochemistry and organic chemistry labs; then no, I am not aware of any all-D proteins. There are a few protein/peptides which include a small number of D-residues, which is marked up to nonribosomal synthesis. The first paper I managed to Google: http://jb.asm.org/content/185/24/7036.full Learning from Nature's Drug Factories: Nonribosomal Synthesis of Macrocyclic Peptides doi: 10.1128/JB.185.24.7036-7043.2003 J. Bacteriol. December 2003 vol. 185 no. 24 7036-7043 If racemic crystallization isn't exciting enough for you, look into quasi-racemic crystallization. On Wed, Feb 15, 2012 at 8:05 AM, David Schuller dj...@cornell.edu wrote: Wukovitz Yeates (1995) Nature Struc. Biol. 2(12): 1062-1067 predicts that the most probable space group for macromolecular crystallization is P -1 (P 1-bar). All you have to do to try it out is synthesize the all-D enantiomer of your protein and get it to fold properly. On 02/14/12 18:36, Prem Kaushal wrote: Hi We have a protein that crystallized in P21212 space group. We are looking for some different crystal forms. We tried few things did not work. Now we are thinking to mutate surface residues. Anybody aware of any software which can predict the mutations that might help in crystallizing protein in different space group, please inform me. Thanks in advance Prem -- === All Things Serve the Beam === David J. Schuller modern man in a post-modern world MacCHESS, Cornell University schul...@cornell.edu -- *** Jacob Pearson Keller Northwestern University Medical Scientist Training Program email: j-kell...@northwestern.edu ***
Re: [ccp4bb] All-D World
G-d is right-handed, so to speak: Ex 15:6 Thy right hand, O LORD, is become glorious in power: thy right hand, O LORD, hath dashed in pieces the enemy. Since we are made in His image, and our (chiral) molecules are the cause of making most of us right-handed, which enantiomer to use was not a real choice but rather flowed logically from His (right-handed) Essence. Our chirality is dictated by His, whatever that means! JPK On Wed, Feb 15, 2012 at 4:48 PM, William G. Scott wgsc...@ucsc.edu wrote: Hi Jacob: After giving this a great deal of reflection ….. I realized that you would face the same paradox that God had to resolve six thousand years ago at the Dawn of Creation, i.e., He needed D-deoxyribose DNA to code for L-amino acid proteins, and vice versa. Likewise, you would probably be faced with a situation where you need L-deoxyribose DNA to code for D-amino acid proteins, so once again, you need a ribozyme self-replicase to escape the Irreducible Complexity(™). (The Central Dogma at least is achiral.) At least it can be done six thousand years, which isn't unreasonable for a Ph.D. thesis project (especially when combined with an M.D.), and you, unlike Him, have access to a Sigma catalogue. All the best, Bill William G. Scott Professor Department of Chemistry and Biochemistry and The Center for the Molecular Biology of RNA 228 Sinsheimer Laboratories University of California at Santa Cruz Santa Cruz, California 95064 USA On Feb 15, 2012, at 10:28 AM, Jacob Keller wrote: So who out there wants to start an all-D microbial culture by total synthesis, a la the bacterium with the synthetic genome a while back? Could it work, I wonder? I guess that would be a certain benchmark for Man's conquest of nature. JPK ps maybe if there is a broadly-acting amino-acid isomerase or set of isomerases of appropriate properties, this could be helpful for getting the culture started--or even for preying on the L world? On Wed, Feb 15, 2012 at 12:17 PM, David Schuller dj...@cornell.edu wrote: On 02/15/12 12:41, Jacob Keller wrote: Are there any all-D proteins out there, of known structure or otherwise? If so, do enantiomer-specific catalyses become inverted? JPK What do you mean by Out There? If you mean in the PDB, then yes. As of two weeks ago, there are ~ 14 racemic structures deposited; most in space group P -1, with one outlier in space group I -4 C 2. This includes RNA, DNA, and PNA, but 6 entries are actually protein. The longest is over 80 residues. Theoretically, enantiomer-specific catalysis ought to be inverted, but most of the structures solved are not enzymes. kaliotoxin, plectasin, antifreeze protein, monellin, villin, and a designed peptide. On the other hand, if by out there you meant in nature outside of biochemistry and organic chemistry labs; then no, I am not aware of any all-D proteins. There are a few protein/peptides which include a small number of D-residues, which is marked up to nonribosomal synthesis. The first paper I managed to Google: http://jb.asm.org/content/185/24/7036.full Learning from Nature's Drug Factories: Nonribosomal Synthesis of Macrocyclic Peptides doi: 10.1128/JB.185.24.7036-7043.2003 J. Bacteriol. December 2003 vol. 185 no. 24 7036-7043 If racemic crystallization isn't exciting enough for you, look into quasi-racemic crystallization. On Wed, Feb 15, 2012 at 8:05 AM, David Schuller dj...@cornell.edu wrote: Wukovitz Yeates (1995) Nature Struc. Biol. 2(12): 1062-1067 predicts that the most probable space group for macromolecular crystallization is P -1 (P 1-bar). All you have to do to try it out is synthesize the all-D enantiomer of your protein and get it to fold properly. On 02/14/12 18:36, Prem Kaushal wrote: Hi We have a protein that crystallized in P21212 space group. We are looking for some different crystal forms. We tried few things did not work. Now we are thinking to mutate surface residues. Anybody aware of any software which can predict the mutations that might help in crystallizing protein in different space group, please inform me. Thanks in advance Prem -- === All Things Serve the Beam === David J. Schuller modern man in a post-modern world MacCHESS, Cornell University schul...@cornell.edu -- *** Jacob Pearson Keller Northwestern University Medical Scientist Training Program email: j-kell...@northwestern.edu *** -- *** Jacob Pearson Keller Northwestern University Medical Scientist Training Program email: j-kell...@northwestern.edu
Re: [ccp4bb] All-D World
Jacob, I wish it were that cheery. Do not forget the darker side of history. The prefix L- stands for levorotary. The levo comes from the Latin wording for left side. Left handedness is also known as sinistrality, from the Latin sinistra which also meant the left side, but over time took on the connotations that we currently associate with the word sinister. The latter word, of course, is generally associated with dark and evil. It is therefore erroneous to attribute the L amino acid to the Almighty. The L amino acid is in fact a diabolical corruption of cellular processes that begin with the D-nucleotide (D- meaning rotating to the right, but derived from dexter, meaning dextrous and skillful). The instrument which causes this perversion of God's perfect righteousness into a sign of evil deserves our strongest moral condemnation... I am referring, of course, to that devilish piece of cellular machinery known as the ribosome. The discovery of the ribosome was a significant blow to the success of what Charles Baudelaire famously called the devil's greatest trick. For years now, his acolytes have attempted to hide the truth about the ribosome by referring to its work with the neutral, innocent-sounding phrase translation. Don't be fooled, but instead pray for the development of the next generation of ribosome inhibitors, or at least dissolve the current generation in holy water before ingesting. -Eric On Feb 15, 2012, at 7:24 PM, Jacob Keller wrote: G-d is right-handed, so to speak: Ex 15:6 Thy right hand, O LORD, is become glorious in power: thy right hand, O LORD, hath dashed in pieces the enemy. Since we are made in His image, and our (chiral) molecules are the cause of making most of us right-handed, which enantiomer to use was not a real choice but rather flowed logically from His (right-handed) Essence. Our chirality is dictated by His, whatever that means! JPK On Wed, Feb 15, 2012 at 4:48 PM, William G. Scott wgsc...@ucsc.edu wrote: Hi Jacob: After giving this a great deal of reflection ….. I realized that you would face the same paradox that God had to resolve six thousand years ago at the Dawn of Creation, i.e., He needed D-deoxyribose DNA to code for L-amino acid proteins, and vice versa. Likewise, you would probably be faced with a situation where you need L-deoxyribose DNA to code for D-amino acid proteins, so once again, you need a ribozyme self-replicase to escape the Irreducible Complexity(™). (The Central Dogma at least is achiral.) At least it can be done six thousand years, which isn't unreasonable for a Ph.D. thesis project (especially when combined with an M.D.), and you, unlike Him, have access to a Sigma catalogue. All the best, Bill William G. Scott Professor Department of Chemistry and Biochemistry and The Center for the Molecular Biology of RNA 228 Sinsheimer Laboratories University of California at Santa Cruz Santa Cruz, California 95064 USA On Feb 15, 2012, at 10:28 AM, Jacob Keller wrote: So who out there wants to start an all-D microbial culture by total synthesis, a la the bacterium with the synthetic genome a while back? Could it work, I wonder? I guess that would be a certain benchmark for Man's conquest of nature. JPK ps maybe if there is a broadly-acting amino-acid isomerase or set of isomerases of appropriate properties, this could be helpful for getting the culture started--or even for preying on the L world? On Wed, Feb 15, 2012 at 12:17 PM, David Schuller dj...@cornell.edu wrote: On 02/15/12 12:41, Jacob Keller wrote: Are there any all-D proteins out there, of known structure or otherwise? If so, do enantiomer-specific catalyses become inverted? JPK What do you mean by Out There? If you mean in the PDB, then yes. As of two weeks ago, there are ~ 14 racemic structures deposited; most in space group P -1, with one outlier in space group I -4 C 2. This includes RNA, DNA, and PNA, but 6 entries are actually protein. The longest is over 80 residues. Theoretically, enantiomer-specific catalysis ought to be inverted, but most of the structures solved are not enzymes. kaliotoxin, plectasin, antifreeze protein, monellin, villin, and a designed peptide. On the other hand, if by out there you meant in nature outside of biochemistry and organic chemistry labs; then no, I am not aware of any all-D proteins. There are a few protein/peptides which include a small number of D-residues, which is marked up to nonribosomal synthesis. The first paper I managed to Google: http://jb.asm.org/content/185/24/7036.full Learning from Nature's Drug Factories: Nonribosomal Synthesis of Macrocyclic Peptides doi: 10.1128/JB.185.24.7036-7043.2003 J. Bacteriol. December 2003 vol. 185 no. 24 7036-7043 If racemic crystallization isn't exciting enough for you, look into quasi-racemic crystallization. On Wed, Feb 15, 2012 at 8:05 AM,
