Using X-Ray Crystallography of the Asp55Asn Mutant of the Phosphatidylcholine-Preferring Phospholipase C from Bacillus Cereus to Support the Mechanistic Role of Asp55 As the General Base

Document Type

Article

Publication Date

9-1-2003

Abstract

Because mutations of the ionizable Asp at position 55 of the phosphatidylcholine preferring phospholipase C from Bacillus cereus (PLCBc) to a non-ionizable Asn generate a mutant enzyme (D55N) with 104-fold lower catalytic activity than the wild-type enzyme, we tentatively identified Asp55 as the general base for the enzymatic reaction. To eliminate the alternate possibility that Asp55 is a structurally important amino acid, the X-ray structures of unbound D55N and complexes of D55N with two non-hydrolyzable substrate analogues have been solved and refined to 2.0, 2.0, and 2.3Å, respectively. The structures of unbound wild-type PLCBc and a wild-type PLCBc-complex with a non-hydrolyzable substrate analogue do not change significantly as a result of replacing Asp55 with Asn. These observations demonstrate that Asp55 is not critical for the structural integrity of the enzyme and support the hypothesis that Asp55 is the general base in the PLCBc-catalyzed hydrolysis of phospholipids.

DOI

10.1016/S0003-9861(03)00343-6

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