Bacillus pasteurii , urease structure

An alternative scenario was put forward based on the crystal structures of urease inhibited by either phosphate, diamidophosphate, or borate (4,5, 28). It gets some support from the kinetic findings for fluoride inhibition of urease (29), as well as from recent model calculations (30, 31). Boric acid, known to be a competitive inhibitor of urease, can be considered a good substrate analogue, since it is isoelectronic with urea and has the same shape and dimension. Bacillus pasteurii could be crystallized in the presence of boric acid. The structure reveals that a molecule of B(OH)3 is symmetrically spanning the nickel ions, replacing Wj, W2,... 

Remaut H, Saeaeov N, Ciueli S and Van Beeu-MEN J (2001) Structural basis for Ni transport and assembly of the urease active site by the metal-lochaperone UreEfrom Bacillus pasteurii. J Biol Chem 276 49365-49370. 

Fig. 1. Structural models of urease from Bacillus pasteurii in the native state (panel A), and its complexes with /3-mercaptoethanol (BME panel B), acetohydroxamic acid (AHA panel C), phosphate (PHO panel D), diamidophosphate (DAP model E), and boric acid (B(0H>3 panel F). The Ni atoms in the active site are shown as filled circles.

Several structures of ureases are available (2). In all cases, the active site contains two Ni(II) ions bridged by the carboxylate group of a carbamylated lysine and by a hydroxide ion (Fig. lA). Each Ni is also coordinated by two histidines and one water molecule, whereas Ni(2) is further bound to an aspartate, resulting in a pentacoordinate Ni(l) and hexacoordinate Ni(2). In the resting state of the enzyme from Bacillus pasteurii, the active site accommodates a fourth water molecule, completing a tetrahedral cluster of solvent molecules (12). The access to the active site is regulated by a flexible helix-loop-helix motif, the position of other amino acids involved in the catalysis being also critically affected by the flap movement. 

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