4G3R: Crystal Structure Of Nitrosyl Cytochrome P450cam

Citation:
Abstract
The crystal structure of the P450cin substrate-bound nitric oxide complex and the substrate-free form have been determined revealing a substrate-free structure that adopts an open conformation relative to the substrate-bound structure. The region of the I helix that forms part of the O(2) binding pocket shifts from an alpha helix in the substrate-free form to a pi 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 a Thr and plays an important role in O(2) activation by participating in an H-bonding network required for O(2) activation. The pi/alpha 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 the substrate-free P450cam structure experiences a similar motion. Most significantly, 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 O(2). The structure of P450cin complexed with nitric oxide, a close mimic of the O(2) complex, shows that Gly238 is likely to form tighter interactions with ligands than the corresponding Gly248 in P450cam. Having a close interaction between an H-bond acceptor, the Gly238 carbonyl O atom, and the distal oxygen atom of O(2) will promote protonation and hence further reduction of the oxy complex to the hydroperoxy intermediate resulting in heterolytic cleavage of the peroxide O-O bond and formation of the active ferryl intermediate required for substrate hydroxylation.
PDB ID: 4G3RDownload
MMDB ID: 101691
PDB Deposition Date: 2012/7/15
Updated in MMDB: 2012/09
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 4G3R: monomeric; determined by author and by software (PISA)
Molecular Components in 4G3R
Label Count Molecule
Protein (1 molecule)
1
Camphor 5-monooxygenase
Molecule annotation
Chemicals (3 molecules)
1
1
2
1
3
1
* Click molecule labels to explore molecular sequence information.

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