Drug Disposition Overview - Pharmacology and at UCSD
Drug Disposition Overview - Pharmacology and at UCSD
Drug Disposition Overview - Pharmacology and at UCSD
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BIOM/PHAR 255 Winter 2013 Halpert - Jan. 17, 2013<br />
Cytochromes P450 (Enzyme<br />
Structures)<br />
Six Protein Regions th<strong>at</strong> Contribute to<br />
Substr<strong>at</strong>e Selectivity: SRS<br />
Substr<strong>at</strong>e Recognition Sites<br />
(SRS)<br />
Gotoh (1992) J. Biol. Chem. 267,<br />
83-90.<br />
SRS1<br />
SRS2<br />
SRS3<br />
SRS4<br />
SRS5<br />
SRS6<br />
heme<br />
2B4<br />
PDB 1SUO<br />
10 of 22<br />
General Structure of Mammalian<br />
Cytochromes P450<br />
Structural<br />
components<br />
alpha helix<br />
beta sheet<br />
heme<br />
protoporphyrin<br />
IX prosthetic<br />
group<br />
2B4<br />
PDB: 1PO5<br />
Major structural fe<strong>at</strong>ures th<strong>at</strong><br />
determine specificity of P450 enzymes<br />
• Length <strong>and</strong> positioning of α−helices <strong>and</strong> βsheets<br />
determines size <strong>and</strong> shape of binding<br />
pocket<br />
• Identity of active site residues determines<br />
binding orient<strong>at</strong>ion of substr<strong>at</strong>es
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