A water sluice is generated in the active site of bovine lens leucine aminopeptidase.
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.
Erhardt
Stefan
S
Institute of Organic and Macromolecular Chemistry, Friedrich Schiller University, Humboldtstrasse 10, D-07743 Jena, Germany.
Jaime
Elke
E
Weston
Jennie
J
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
D007931:Leucyl Aminopeptidase