Role of the conserved distal heme asparagine of coral allene oxide synthase (Asn137) and human catalase (Asn148): mutations affect the rate but not the essential chemistry of the enzymatic transformations.

Abstract:

:A catalase-related allene oxide synthase (cAOS) and true catalases that metabolize hydrogen peroxide have similar structure around the heme. One of the distal heme residues considered to help control catalysis is a highly conserved asparagine. Here we addressed the role of this residue in metabolism of the natural substrate 8R-hydroperoxyeicosatetraenoic acid by cAOS and in H(2)O(2) breakdown by catalase. In cAOS, the mutations N137A, N137Q, N137S, N137D, and N137H drastically reduced the rate of reaction (to 0.8-4% of wild-type), yet the mutants all formed the allene oxide as product. This is remarkable because there are many potential heme-catalyzed transformations of fatty acid hydroperoxides and special enzymatic control must be required. In human catalase, the N148A, N148S, or N148D mutations only reduced rates to approximately 20% of wild-type. The distal heme Asn is not essential in either catalase or cAOS. Its conservation throughout evolution may relate to a role in optimizing catalysis.

journal_name

Arch Biochem Biophys

authors

Gao B,Boeglin WE,Brash AR

doi

10.1016/j.abb.2008.07.011

subject

Has Abstract

pub_date

2008-09-15 00:00:00

pages

285-90

issue

2

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(08)00349-4

journal_volume

477

pub_type

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