2bhb: Difference between revisions

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[[Image:2bhb.jpg|left|200px]]
{{Seed}}
[[Image:2bhb.png|left|200px]]


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{{STRUCTURE_2bhb|  PDB=2bhb  |  SCENE=  }}  
{{STRUCTURE_2bhb|  PDB=2bhb  |  SCENE=  }}  


'''ZN SUBSTITUTED E. COLI AMINOPEPTIDASE P'''
===ZN SUBSTITUTED E. COLI AMINOPEPTIDASE P===




==Overview==
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The effect of metal substitution on the activity and structure of the aminopeptidase P (APPro) from Escherichia coli has been investigated. Measurements of activity in the presence of Mn2+, Mg2+, Zn2+, Na+, and Ca2+ show that significant activity is seen only in the Mn-bound form of the enzyme. The addition of Zn2+ to [MnMn(APPro)] is strongly inhibitory. Crystal structures of [MnMn(APPro)], [MgMg(APPro)], [ZnZn(APPro)], [ZnMg(APPro)], [Ca_(APPro)], [Na_(APPro)], and [apo(APPro)] were determined. The structures of [Ca_(APPro)] and [Na_(APPro)] have a single metal atom at their active site. Surprisingly, when a tripeptide substrate (ValProLeu) was soaked into [Na_(APPro)] crystals in the presence of 200 mM Mg2+, the structure had substrate, but no metal, bound at the active site. The structure of apo APPro complexed with ValProLeu shows that the N-terminal amino group of a substrate can be bound at the active site by carboxylate side chains that normally bind the second metal atom, providing a model for substrate binding in a single-metal active enzyme. Structures of [MnMn(APPro)] and [ZnZn(APPro)] complexes of ProLeu, a product inhibitor, in the presence of excess Zn reveal a third metal-binding site, formed by two conserved His residues and the dipeptide inhibitor. A Zn atom bound at such a site would stabilize product binding and enhance inhibition.
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{{ABSTRACT_PUBMED_16229471}}


==About this Structure==
==About this Structure==
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[[Category: Pita-bread fold]]
[[Category: Pita-bread fold]]
[[Category: Proline-specific peptidase]]
[[Category: Proline-specific peptidase]]
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