PMID:15388923
| Citation |
Graham, SC, Maher, MJ, Simmons, WH, Freeman, HC and Guss, JM (2004) Structure of Escherichia coli aminopeptidase P in complex with the inhibitor apstatin. Acta Crystallogr. D Biol. Crystallogr. 60:1770-9 |
|---|---|
| Abstract |
Aminopeptidase P (APPro) is a metalloprotease whose active site includes a dinuclear manganese(II) cluster. The enzyme cleaves the N-terminal residue from a polypeptide when the second residue is proline. A complex of Escherichia coli APPro (EcAPPro) with an inhibitor, apstatin [N-(2S,3R)-3-amino-2-hydroxy-4-phenyl-butanoyl-L-prolyl-L-prolyl-L-alaninamide], has been crystallized. Apstatin binds to the active site of EcAPPro with its N-terminal amino group coordinated to one of the two Mn(II) atoms at the metal centre. The apstatin hydroxyl group replaces a hydroxide ion which bridges the two metal atoms in the native enzyme. The first proline residue of apstatin lies in a small hydrophobic cleft. The structure of the apstatin-EcAPPro complex has been refined at 2.3 A resolution with residuals R = 0.179 and R(free) = 0.204. The structure of the complex illustrates how apstatin inhibits APPro and suggests how substrates may bind to the enzyme, but the basis of the proline-specificity remains elusive. |
| Links |
PubMed Online version:10.1107/S0907444904018724 |
| Keywords |
Amino Acid Sequence; Aminopeptidases/antagonists & inhibitors; Aminopeptidases/chemistry; Binding Sites; Catalysis; Crystallography, X-Ray; Escherichia coli/enzymology; Hydroxides/chemistry; Ions; Manganese/chemistry; Models, Chemical; Models, Molecular; Molecular Sequence Data; Peptides/chemistry; Proline/chemistry; Protein Binding; Protein Conformation; Protein Structure, Secondary; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Software |
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