Re: [ccp4bb] Bidentate GLU vs two monodentate GLU in metalloproteins
Hi, I would expect that the principal issue is that (bis)mono and bidentate iron complexes are likely to have different chemistries, even though they would have the same number of oxygen atoms nearby the iron atom – For example, unlike two monodentate carboxylates, the shape of a bidentate carboxylate is unlikely to allow the oxygen atoms to coordinate in an idealised octahedral or tetrahedral orientation at the iron atom. So I’d expect that metalloenzymes would simply evolve to have carboxylates with the correct denticity (or capacity to cycle between mono and bidentate) to catalyse their reactions. Here’s an article that discusses this in one particular case of methane monooxygenase (with glutamates providing the carboxylate ligands) Mikael A. Miniera and Stephen J. Lippard, Dalton Trans 2015, 44, 18111 DOI: 10.1039/C5DT02138C Ian From: CCP4 bulletin board On Behalf Of Chandra Prakash Tiwari Sent: 18 July 2019 17:07 To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Bidentate GLU vs two monodentate GLU in metalloproteins [EXTERNAL] Dear all, What is more preferable or conserved by evolution of lifeform point of view between glutamate acting as bidentate ligand by its carboxylate group or two monodentate GLU at metal binding site in natural metalloenzymes. I was thinking 2 GLU are better than one bidentate GLU because if one GLU gets mutated other GLU will still be able to form a coordination bond to a metal. Please comment and help if i am right or wrong. metal is Fe2+. In short which will evolve with time a bidentate GLU or 2 monodentate GLU. To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB=1 STATEMENT OF CONFIDENTIALITY. This email and any attachments may contain confidential, proprietary, privileged and/or private information. If received in error, please notify us immediately by reply email and then delete this email and any attachments from your system. Thank you! https://www.evotec.com/en/about/site-information/data-protection-uk Evotec (UK) Ltd is a limited company registered in England and Wales. Registration number:2674265. Registered office: 114 Innovation Drive, Milton Park, Abingdon, Oxfordshire, OX14 4RZ, United Kingdom. To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB=1
[ccp4bb] Bidentate GLU vs two monodentate GLU in metalloproteins
Dear all, What is more preferable or conserved by evolution of lifeform point of view between glutamate acting as bidentate ligand by its carboxylate group or two monodentate GLU at metal binding site in natural metalloenzymes. I was thinking 2 GLU are better than one bidentate GLU because if one GLU gets mutated other GLU will still be able to form a coordination bond to a metal. Please comment and help if i am right or wrong. metal is Fe2+. In short which will evolve with time a bidentate GLU or 2 monodentate GLU. To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB=1
Re: [ccp4bb] Bidentate GLU vs two monodentate GLU in metalloproteins
Hi Chandra, That is an intriguing question. The problem is that even if you would data mine this, the data in the PDB would be incredibly skewed to whatever we managed to crystalise. And then there is the problem of poorly modeled metal sites. So the true answer will be elusive. Purely anecdotal, I tend to see more monodentate metal binding in protein structures. Apart from confirmation bias, it might be caused by bidentate coordination almost always having suboptimal geometry in terms of orbital overlap. Another issue is that monodentate binding is more evolutionary robust. In many metal sites you don’t need direct charge compensation by a formal charge. Polarisation is quite enough. That means that your coordinating oxygen can be replaced by quite a few residues. This is not the case in a bidentate setup. HTH, Robbie From: CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] On Behalf Of Chandra Prakash Tiwari Sent: Monday, July 15, 2019 12:44 To: CCP4BB@JISCMAIL.AC.UK Subject: [ccp4bb] Bidentate GLU vs two monodentate GLU in metalloproteins Dear all, What is more preferable or conserved by evolution point of view between glutamate acting as bidentate ligand by its carboxylate group or two monodentate GLU at metal binding site in natural metalloprotein. I was thinking 2 GLU are better than one bidentate GLU because if one GLU gets mutated other GLU will still be able to form a coordination bond to a metal. Please comment and help if i am right or wrong. To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB=1 To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB=1
[ccp4bb] Bidentate GLU vs two monodentate GLU in metalloproteins
Dear all, What is more preferable or conserved by evolution point of view between glutamate acting as bidentate ligand by its carboxylate group or two monodentate GLU at metal binding site in natural metalloprotein. I was thinking 2 GLU are better than one bidentate GLU because if one GLU gets mutated other GLU will still be able to form a coordination bond to a metal. Please comment and help if i am right or wrong. To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=CCP4BB=1
