(Don't know if this should go to developers or the list. Some users may have
more information, or be interested in the information.)
I'd like to point out what i believe to be errors in the HEC.cif file released
with
CCP4 version 6.2 and later.
HEC is heme c which is regular heme as in hemoglobin (heme b) that has been
covalently linked to the protein by two cysteine SH groups adding across the
double bonds (CAx-CBx) in the two vinyl substituents. Thus heme c by itself
does not exist, only in the structure of a protein. This may make problems
for programs autogenerating the parameters for the ligand.
The S atom becomes attached to CAx which thus becomes sp3. CBx also becomes sp3.
(x here is b or c to distinguish the vinyl groups on pyrrole rings b and c.
Link to atom names is: http://xray.bmc.uu.se/hicup/HEC/hec_chempdb.gif)
in -6.1.3 this is clear from the angles about CAx:
HEC C3B CAB CBB 109.000 3.000
HEC C3B CAB HAB 109.000 3.000
HEC HAB CAB CBB 109.000 3.000
and bonds:
HEC C3B CAB coval 1.544 0.020
HEC CAB CBB coval 1.544 0.020
in -6.4 this has become planar
HEC C3B CAB HAB 120.000 3.000
HEC C3B CAB CBB 120.000 3.000
HEC HAB CAB CBB 120.000 3.000
HEC CAB C3B double 1.483 0.020
HEC CBB CAB single 1.510 0.020
Another apparent discrepancy has to do with C-C bond lengths in the pyrrole
rings of the porphyrin.
First, all rings should be the same. if you draw conjugated double bonds
as in the diagrams on the wikipedia heme page http://en.wikipedia.org/wiki/Heme
then three of the pyrrole rings have a double bond in the side apposite N,
while the third has a single.
HEC.cif in -6.1.3 (incorrecrly) reflected this pattern:
HEC C2A C3A coval 1.334 0.020
HEC C2B C3B coval 1.334 0.020
HEC C2C C3C coval 1.334 0.020
HEC C3D C2D coval 1.544 0.020
But the porphrin ring is 4-fold symmetric, presumably
a resonance hybrid of structures with the single bond on different rings.
so the bond opposite N is 3 parts double to 1 part single in all 4 rings.
On the other hand the bonds from the N-adjacent carbons to the outer carbons
(C1x-C2x and C3x-C4x) are single in three of the rings and double in one ring
(in any one resonance structure) so 1 part double to 3 parts single.
The heme params we used to use with CNS/Xplor seem consistent with this 1/4 3/4
hybridization:
atomtype bond explanation
FE - NP 1.96 (Fe-N)
NP -CPA 1.38 (N to inner C atoms)
CPA-CPB 1.44 (inner to outer C)
CPB-CPB 1.36 (between the outer C)
CPA-CPM 1.37 (CPM are the bridging carbons)
These are from toph19/param19.rcv which I see are available online at
http://www.msg.ucsf.edu/local/programs/xplor/tutorial.dir/toppar/toph19.rcv
http://www.msg.ucsf.edu/local/programs/xplor/tutorial.dir/toppar/param19.rcv
And these are apparently the parameters used by Huber's group in the
award-winning work on photosynthetic reaction center which contains c
cytochromes.
The heme parameters are from Kuriyan's earlier work on MGb, 1MBC.pdb (1.5 A),
the parameters being from table 1 of
KITAGAWA, ABE AND OGOSHI J.C.P. 69, (1978) PAGES 4526-4534
which is from a small-mol structure of Ni-octaethyl porphyrin
ccp4-6.4 corrects the asymmetric porphyrin ring, but with all C-C bonds
in all pyrrole rings pegged at 1.490 A instead of 1.44, 1.36 as above.
There is an atomic-resolution structure of a cytochrome c (1C75, 0.95 A).
which contains a heme c (denoted HEM not HEC- HEC was introduced later,
originally for nmr structures). The C-C bonds in this structure support
the two different types used by kurriyan:
HEME C from 1C75 x= A B C D
atomtype kuriyan bond
FE - NP 1.958 FE-Nx 2.00 1.97 1.99 1.97
NP -CPA 1.376 Nx-C1x 1.37 1.3? 1.40 1.38 \
Nx-C4x 1.37 1.38 1.37 1.35 |
CPA-CPB 1.443 C1X-C2x 1.44 1.44 1.44 1.45 |ring
C4x-C3x 1.45 1,45 1.43 1.47 |
CPB-CPB 1.346 C2x-C3x 1.36 1.36 1.34 1.35 /
Needless to say the current validation report for 1C75 shows very bad
ligand geometry, first because it uses HEM instead of HEC, second because
the bonds within the porphrin are different.
So should the C-C bonds be all equal, or fall in two classes?
================================================================
Included below are summaries of various parameters/measurements of
heme bond lengths on the off chance that someone might be interested.
Second column are the values from param19.rcv for the bond type
Columns labeled A, B, C, D are the actual values or parameters for atoms in
that (ABCD) pyrrole ring.
================================================================
HEME C from 1C75 x= A B C D
atomtype Kuriyan atoms
FE - NP 1.958 FE-Nx 2.00 1.97 1.99 1.97
NP -CPA 1.376 Nx-C1x 1.37 1.3? 1.40 1.38 \
Nx-C4x 1.37 1.38 1.37 1.35 |
CPA-CPB 1.443 C1X-C2x 1.44 1.44 1.44 1.45 |ring
C4x-C3x 1.45 1,45 1.43 1.47 |
CPB-CPB 1.346 C2x-C3x 1.36 1.36 1.34 1.35 /
CPA-CPM 1.371 C1x-CHw 1.39 1.39 1.36 1.39 \bridge
C4x-CHy 1.38 1.38 1.38 1.40 /
methyl:
CPB-CH3E 1.52 C2x-CMx 1.50 1.51 1.49 \Methyl
C3x-CMx 1.49 /
Vinyls:
CPB-CR1E 1.38* C3x-CAx 1.50 1.52 \Vinyl
CR1E-CH2E 1.52* CAx-CBx 1.55 1.56 /
*OK for heme C, should be double for PP9
CPB-CH2E C2x-CAx 1.50 \
C3x-CAx 1.52 |
CH2E-CH2E CAx-CBx 1.55 1.59 |propionate
CH2E-C CBx-C 1.41 1.41 |
CGx-O1x 1.25 1.27 |
CGx-O2x 1.29 1.26 |
C-O? CGx-O1x 1.25 1.27 |
CGx-O2x 1.29 1.26 /
1C75 is 0.97 A!
================================================================
HEME from 1MBC x= A B C D
FE - NP 1.958 FE-Nx 1.99 1.90 1.99 2.0
NP -CPA 1.376 Nx-C1x 1.37 1.42 1.40 1.37
Nx-C4x 1.42 1.39 1.35 1.39
CPA-CPB 1.443 C1X-C2x 1.49 1.42 1.40 1.52
C4x-C3x 1.51 1.47 1.47 1.42
CPB-CPB 1.346 C2x-C3x 1.33 1.31 1.35 1.34
CPA-CPM 1.371 C1x-CHw 1.35 1.40 1.33 1.36
C4x-CHy 1.45 1.38 1.40 1.41
methyl:
CPB-CH3E 1.52 C2x-CMx 1.57 1.55 1.56
C3x-CMx 1.55
Vinyls:
CPB-CR1E 1.38* C3x-CAx 1.52 1.59
CR1E-CH2E 1.52* CAx-CBx 1.37 1.31
* it appears these two parameters have been switched!
CPB-CH2E C2x-CAx 1.51 1.54
C3x-CAx
CH2E-CH2E CAx-CBx 1.55 1.52
CH2E-C CBx-CGx 1.51 1.43
C-O? CGx-O1x 1.28 1.30
CGx-O2x 1.30 1.21
================================================================
HEM.cif fr phenix-dev-1745 x= A B C D
FE - NP 1.958 FE-Nx 2.080 2.080 2.080 2.080
NP -CPA 1.376 Nx-C1x 1.384 1.384 1.384 1.384
Nx-C4x 1.384 1.384 1.384 1.384
CPA-CPB 1.443 C1X-C2x 1.449 1.449 1.449 1.449
C4x-C3x 1.449 1.449 1.449 1.449
CPB-CPB 1.346 C2x-C3x 1.334 1.334 1.334 1.334* was 1.544
CPA-CPM 1.371 C1x-CHw 1.378 1.378 1.378 1.378
C4x-CHy 1.378 1.378 1.378 1.378
methyl:
CPB-CH3E 1.52 C2x-CMx 1.544 1.544 1.544
C3x-CMx 1.544
Vinyls:
CPB-CR1E 1.38* C3x-CAx 1.544 1.544
CR1E-CH2E 1.52* CAx-CBx 1.337 1.337
CPB-CH2E C2x-CAx 1.544
C3x-CAx 1.544
CH2E-CH2E CAx-CBx 1.525 1.525
CH2E-C CBx-CGx 1.506 1.506
C-O? CGx-O1x 1.258 1.258
CGx-O2x 1.258 1.258
$ diff /v1/sw/lnx/phenix-1.8.1-1168/chem_data/mon_lib/h/HEM.cif
/v1/sw/lnx/phenix-dev-1745/chem_data/mon_lib/h/HEM.cif
244c244
< HEM C3D C2D coval 1.544 0.020
---
HEM C3D C2D coval 1.334 0.020
[
================================================================
HEM.cif from ccp4 6.4.0 x= A B C D range
Ring:
FE - NP 1.958 FE-Nx 1.977 2.093 2.088 1.845 1.845-2.093
NP -CPA 1.376 Nx-C1x 1.378 1.334 1.377 1.333 1.333-1.378
Nx-C4x 1.377 1.335 1.377 1.335
CPA-CPB 1.443 C1X-C2x 1.408 1.421 1.404 1.469 1.404-1.482
C4x-C3x 1.410 1.482 1.421 1.469
CPB-CPB 1.346 C2x-C3x 1.359 1.365 1.384 1.352 1.352-1.384
CPA-CPM 1.371 C1x-CHx 1.389 1.400 1.392 1.401 1.383-1.401
C4x-CHy 1.386 1.393 1.383 1.398
Methyls
CPB-CH3E 1.52 C2x-CMx 1.507 1.508 1.507 1.507-1.508
C3x-CMx 1.507
Vinyls:
CPB-CR1E 1.38* C3x-CAx 1.474 1.474 1.474
CR1E-CH2E 1.52* CAx-CBx 1.330 1.329 1.329-1.330
Propionates:
CPB-CH2E C2x-CAx 1.506 1.506
C3x-CAx 1.506
CH2E-CH2E CAx-CBx 1.530 1.529 1.529-1.530
CH2E-C CBx-CGx 1.506 1.507 1.506-1.507
C-O? CGx-O1x 1.251 1.251 1.251
CGx-O2x 1.251 1.251
================================================================
HEM from PDB x= A B C D
FE - NP 1.958 FE-Nx ---- 1.95 1.95 1.95
NP -CPA 1.376 Nx-C1x
Nx-C4x 1.38
CPA-CPB 1.443 C1X-C2x 1.43 1.45 1.45
C4x-C3x 1.43 1.45 1.45 1.44
CPB-CPB 1.346 C2x-C3x ---- 1.45 1.45 1.43 C3C-C2C ideal is 1.45 in my
report, 1.43 in 1c75 report
CPA-CPM 1.371 C1x-CHw
C4x-CHy
methyl:
CPB-CH3E 1.52 C2x-CMx ---- 1.45 1.45 1.45
C3x-CMx
Vinyls:
CPB-CR1E 1.38* C3x-CAx ---- 1.40 1.40
CR1E-CH2E 1.52* CAx-CBx
CPB-CH2E C2x-CAx
C3x-CAx
CH2E-CH2E CAx-CBx
CH2E-C CBx-CGx
C-O? CGx-O1x
CGx-O2x
================================================================
HEC from PDB x= A B C D
FE - NP 1.958 FE-Nx 1.92 1.92 1.92 1.92
NP -CPA 1.376 Nx-C1x
Nx-C4x 1.36
CPA-CPB 1.443 C1X-C2x 1.42 1.43 1.43 1.43
C4x-C3x 1.42 1.42 1.42 1.43 HEC C3C-C4C 1.42
CPB-CPB 1.346 C2x-C3x 1.37 1.42 1.40 1.37
CPA-CPM 1.371 C1x-CHw 1.37 1.39 1.39 1.39
C4x-CHy 1.37 1.37 1.37 1.39
methyl:
CPB-CH3E 1.52 C2x-CMx
C3x-CMx
Vinyls:
CPB-CR1E 1.38* C3x-CAx ---- 1.34 1.34
CR1E-CH2E 1.52* CAx-CBx
CPB-CH2E C2x-CAx
C3x-CAx
CH2E-CH2E CAx-CBx
CH2E-C CBx-CGx
C-O? CGx-O1x
CGx-O2x
================================================================
HEC from ccp6.4 x= A B C D
FE - NP 1.958 FE-Nx 2.090 2.090 2.090 2.090
NP -CPA 1.376 Nx-C1x 1.337 1.337 1.337 1.337
Nx-C4x 1.337 1.337 1.337 1.337
CPA-CPB 1.443 C1X-C2x 1.490 1.490 1.490 1.490
C4x-C3x 1.490 1.490 1.490 1.490
CPB-CPB 1.346 C2x-C3x 1.490 1.490 1.490 1.490 (1.334/1.544 in 6.1.3)
CPA-CPM 1.371 C1x-CHw 1.483 1.483 1.483 1.483
C4x-CHy 1.483 1.483 1.483 1.483
methyl:
CPB-CH3E 1.52 C2x-CMx 1.506 1.506
C3x-CMx 1.506 1.506
Vinyls:
CPB-CR1E 1.38* C3x-CAx 1.483 1.483 (1.544 in 6.1.3)
CR1E-CH2E 1.52* CAx-CBx 1.510 1.510 (1.544 in ")
CPB-CH2E C2x-CAx 1.510 1.510
C3x-CAx
CH2E-CH2E CAx-CBx 1.524 1.524
CH2E-C CBx-CGx 1.510 1.510
C-O? CGx-O1x 1.250 1.250
CGx-O2x 1.250 1.250
HEC C3B CAB HAB 120.000 3.000
HEC C3B CAB CBB 120.000 3.000
HEC HAB CAB CBB 120.000 3.000
================================================================
HEC from Phenix-dev-1745 x= A B C D
FE - NP 1.958 FE-Nx 2.080 2.080 2.080 2.080
NP -CPA 1.376 Nx-C1x 1.384 1.384 1.384 1.384
Nx-C4x 1.384 1.384 1.384 1.384
CPA-CPB 1.443 C1X-C2x 1.449 1.449 1.449 1.449
C4x-C3x 1.449 1.449 1.449 1.449
CPB-CPB 1.346 C2x-C3x 1.334 1.334 1.334 1.544
CPA-CPM 1.371 C1x-CHw 1.378 1.378 1.378 1.378
C4x-CHy 1.378 1.378 1.378 1.378
methyl:
CPB-CH3E 1.52 C2x-CMx 1.544 1.544 1.544
C3x-CMx 1.544
Vinyls:
CPB-CR1E 1.38* C3x-CAx 1.544 1.544
CR1E-CH2E 1.52* CAx-CBx 1.544 1.544
CPB-CH2E C2x-CAx 1.544
C3x-CAx 1.544
CH2E-CH2E CAx-CBx 1.525 1.525
CH2E-C CBx-CGx 1.506 1.506
C-O? CGx-O1x 1.258 1.258
CGx-O2x 1.258 1.258
HEC C3B CAB CBB 109.000 3.000
HEC C3B CAB HAB 109.000 3.000
HEC HAB CAB CBB 109.000 3.000
================================================================
