1PHA

INHIBITOR-INDUCED CONFORMATIONAL CHANGE IN CYTOCHROME P450-CAM

1PHA の概要

• エントリーDOI: 10.2210/pdb1pha/pdb
• 分子名称: CYTOCHROME P450-CAM, PROTOPORPHYRIN IX CONTAINING FE, 1-(N-IMIDAZOLYL)-2-HYDROXY-2-(2,3-DICHLOROPHENYL)OCTANE, ... (4 entities in total)
• 機能のキーワード: oxidoreductase(oxygenase)
• 由来する生物種: Pseudomonas putida
• 細胞内の位置: Cytoplasm : P00183
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 47546.64

構造登録者

Poulos, T.L. (登録日: 1992-07-27, 公開日: 1993-10-31, 最終更新日: 2024-02-14)

主引用文献

Raag, R.,Li, H.,Jones, B.C.,Poulos, T.L.
Inhibitor-induced conformational change in cytochrome P-450CAM.
Biochemistry, 32:4571-4578, 1993

PubMed Abstract: The X-ray crystal structures of cytochrome P-450CAM complexed with both enantiomers of a chiral, multifunctional inhibitor have been refined to R-factors of 21.0% [(+)-enantiomer] and 19.6% [(-)-enantiomer] at approximately 2.1-A resolution. Binding of either enantiomer, both considerably larger than the natural substrate camphor, results in similar, dramatic structural changes in the enzyme. In contrast to all previous P-450CAM crystallographic structures, the Tyr96 side chain is not pointing "down" toward the heme but is rather directed "up" into the proposed substrate access channel. This conformational change is accompanied by the displacement of the Phe193 side chain out into the solvent at the enzyme surface. These changes are consistent with the assignment of this region of the enzyme as the access channel [Poulos et al. (1986) Biochemistry 25, 5314-5322] and suggest that several aromatic residues lining the channel may be involved in substrate recognition and channeling to the active site. The cation usually observed coordinated to the Tyr96 carbonyl oxygen is missing in the presence of the (+)-enantiomer but is present with the (-)-enantiomer. The Phe87 side chain, located near the inhibitor binding site, adopts different orientations depending upon which enantiomer is bound. Finally, electron density reveals that although the inhibitor enantiomers were dichlorinated as provided, when bound to P-450CAM the chlorine atoms are present at only 0-20% occupancy, probably reflecting selective binding of impurities in the samples. Coordinates of these inhibited P-450CAM complexes have been deposited in the Brookhaven Protein Data Bank [Bernstein et al. (1977) J. Mol. Biol. 112, 535-542].

PubMed: 8485133
DOI: 10.1021/bi00068a013

実験手法

X-RAY DIFFRACTION (1.63 Å)