1. One unit cell showing four P450 cam F87W/Y96F/V247L/C334A mutants
2. One wireframe P450 molecule with heme and inhibitor 1,3,5-TRICHLOROBENZENE
3. A ribbon representation
4. A ribbon view with the I-Helix blue, the L-Helix magenta and the inhibitor green
Cys357 = yellow
5. G248, G249, D251 and T252 around the oxygen binding pocket
6. D251 and R186 linking the F-helix to the I-helix
7. D251 and R186 with K178 linking the F-helix to the I-helix and kinking the I-helix
8. The C-helix residues R112 and Q108 coordinating a heme propionate group. This is the WXXXR equivalent in P450 cam (CYP101).
9a. Closeup spacefill view R112 Q108 of P450cam
9b. Closeup spacefill view R124 W120 of CYP2C5, the mammalian structure in the same region
10. His 355 coordinates the other oxygen on the heme propionate R112 Q108 H355 C357
11. Closeup of His 355 coordinating the other oxygen on the heme propionate R112 Q108. His 355 is shown in CPK colors.
12. Long range view of the sidechains of Asp297 and Arg299 coordinating the other heme propionate group.
13. Closeup view of the sidechains of Asp297 and Arg299 coordinating the other heme propionate group. The 5 stranded beta sheet from the beta rich part of the p450 is shown in yellow.
14. Closeup view of the turn between the I-helix and the J-helix. Pro268 is shown in yellow.
15. Closeup view of F263 in contact with H270 and V338. The Phe263 is at a conserved position often occupied by an aromatic sidechain in the I-helix.
16. Closeup view of the PERF Arg342 forming a charge triad with Glu287 and Arg290 of the EXXR motif in the K-helix. Arg342 and Arg290 are shown in CPK colors. F263, H270 and V338 are still present from view 15.
17. Closeup view of the charge triad capped with three carbonyls from adjacent amino acids, A333, A334 and P335.
18. Closeup view of the charge triad from the wild type sequence in the same orientation. Note that the carbonyl crown looks the same and it does not seem to matter what sidechains are facing out. However, This may be critical for interaction with other proteins.
19. A view of the KYG motif and the proline rich motif (PPGPTPFPIIGNI in CYP2C5). These are close in space, with P33T34 touching the KYG tyrosine.
20. A view of the whole 2C5 P450 with the FPIIGNI turn highlighted. The I-helix is magenta for a reference point.
21. A view of the PKG motif of CYP2C5 with YFIPKG 376-381 and VRFRN 370-375 highlighted. Beta 1-4 (366-369) is violet and beta 1-3 (382-387) is orange. The I-helix is magenta for a reference point. This hairpin loop is equivalent to beta-2 in P450 cam. The FPIIGNI loop is shown in yellow
22. A view of the PKG motif of P450 cam with VQLKKG 376-381 and YEFHG 370-375 highlighted. Beta 1-4 is violet and beta 1-3 is orange. The I-helix is magenta for a reference point. This hairpin loop is beta-2 in P450 cam.
23. A view of the heme and the loop containing the heme signature sequence. F350-C357. (Gly 359 is at the start of the L-helix and it is not included here.)
24. A view of the heme and the loop containing the heme signature sequence. F350-C357. Phe350 is shown in spacefill to illustrate the close contact to the heme surface. F350 is the first amino acid in the heme signature.
25. A view of the heme and the loop containing the heme signature sequence. F350-C357. Cys357 is added in spacefill to illustrate the close contact to the Phe350.
26. A view of the heme and the loop containing the heme signature sequence. F350-C357. Gly353 is shown in white as one of the other conserved amino acids in this signature. It permits a sharp turn in the sequence at this point.
27. A view of the heme and the loop containing the heme signature sequence. F350-C357. Val356 is shown to illustrate how it fills the space between Gly353 and Cys357
28. A view of the heme and the loop containing the heme signature sequence. F350-C357. His355 is shown again (see above for its contact with one of the heme propionates). This time its role in the heme signature is emphasized.
29. A view of the heme and the E-helix, showing the contact between the conserved Ile178 and a heme vinyl group.
30. A view of the heme the E-helix, and the I-helix. The I-helix lies in a groove between the heme and the E-helix.
31. The same as view 29 with Asn176 colored orange. This is equivalent to the conserved Asp in DIIC. (see views 34 and 35 for more on Asn176)
32. The same as view 29 with Ile178, Cys179, Ile182 and Phe183 colored cyan. These residues form a hydrophobic pocket for Phe292 of the I-helix.
33. A view of Phe292 on the I-helix (wireframe) binding into the hydrophobic pocket of the E-helix (white). F292 is in the sequence FGAGTET.
34. A view of CYP2C5 with helix D, helix E and helix F coloured for orientation.
35. A closeup view of helices D, E and F showing the charge pair between Glu 148 on D and Arg186 from the loop between helices E and F. The Asn176 group from the E-helix is interacting with this charge pair. Carboxyl and guanidinium groups are in CPK colors.
36a. The last view is appropriately of the end of the CYP2C5 sequence. This view shows that the end of this p450 sequence 480-487 interacts with the loop between helix D and helix E amino acids 159-167. Actual contact is limited to 480-485 and 161-166.
36b. This view shows the other beta strand 453-458 in white spacefill. 480-485, helix D and helix E amino acids 161-166.
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