title: A water sluice is generated in the active site of bovine lens leucine aminopeptidase.
abstract: Nature has provided the binuclear zinc based active site of bovine lens leucine aminopeptidase (blLAP) with two water channels: one for substrate docking and a much smaller one (function unknown) above Zn1. In addition, Zn1 possesses an unusual pentacoordinate geometry with a loosely bound carbonyl ligand (Ala333). Extensive DFT calculations on a model of the active site provide first mechanistic implications for these structural features. The weakly bound carbonyl ligand is capable of functioning as a "traffic cop" to direct water molecules coming from the small channel into the heart of the active site. A water sluice is thus generated that is capable of repeatedly providing a series of nucleophilic active "Zn-OH" functionalities.
authors.affiliation: Institute of Organic and Macromolecular Chemistry, Friedrich Schiller University, Humboldtstrasse 10, D-07743 Jena, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Erhardt
authors.forename: Elke
authors.initials: E
authors.lastname: Jaime
authors.forename: Jennie
authors.initials: J
authors.lastname: Weston
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D007700:Kinetics; D007908:Lens, Crystalline / Q000201:enzymology*; D007931:Leucyl Aminopeptidase / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D013816:Thermodynamics
chemical_list: D007931:Leucyl Aminopeptidase