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Publication Abstract from PubMed

The crystal structure of the P450cin substrate-bound nitric oxide complex and the substrate-free form have been determined. The substrate-free structure adopts an open conformation relative to the substrate-bound structure. The region of the I helix that forms part of the O2 binding pocket shifts from a-helix in the substrate-free form to a p helix in the substrate-bound form. Unique to P450cin is an active site residue, Asn242, in the I helix that H-bonds with the substrate. In most other P450s this residue is Thr which plays an important role in O2 activation by participating in a H-bonding network required for O2 activation. The p/a I helix transition results in the carbonyl O atom of Gly238 moving in to form an H-bond with the water/hydroxide ligand in the substrate-free form. The corresponding residue, Gly248, in P450cam experiences a similar motion and in the oxy-P450cam complex Gly248 adopts a position midway between the substrate-free and -bound states. A comparison between these P450cam and the new P450cin structures provides insights into differences in how the two P450s activate O2. In P450cin, NO and presumably O2, is positioned closer to Gly238 relative to how ligands bind in P450cam. This indicates that Gly238 forms a tighter interaction with diatomic ligands and is the key protein component in the active site that encourages reduction and protonation of the iron-linked O2 by accepting an H-bond from the hydroperoxy intermediate.

Crystal Structures of Substrate-Free and Nitrosyl Cytochrome P450cin: Implications for O2 Activation.,Madrona Y, Tripathi S, Li H, Poulos TL Biochemistry. 2012 Jul 9. PMID:22775403^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.