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The structure, function and properties of sirohaem decarboxylase – an enzyme with structural homology to a transcription factor family that is part of the alternative haem biosynthesis pathway
Author(s) -
Palmer David J.,
Schroeder Susanne,
Lawrence Andrew D.,
Deery Evelyne,
Lobo Susana A.,
Saraiva Ligia M.,
McLean Kirsty J.,
Munro Andrew W.,
Ferguson Stuart J.,
Pickersgill Richard W.,
Brown David G.,
Warren Martin J.
Publication year - 2014
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12656
Subject(s) - biology , homology (biology) , transcription factor , enzyme , genetics , function (biology) , biochemistry , transcription (linguistics) , biosynthesis , computational biology , gene , linguistics , philosophy
Summary Some bacteria and archaea synthesize haem by an alternative pathway, which involves the sequestration of sirohaem as a metabolic intermediate rather than as a prosthetic group. Along this pathway the two acetic acid side‐chains attached to C1 2 and C1 8 are decarboxylated by sirohaem decarboxylase, a heterodimeric enzyme composed of AhbA and AhbB , to give didecarboxysirohaem. Further modifications catalysed by two related radical SAM enzymes, AhbC and AhbD , transform didecarboxysirohaem into Fe‐coproporphyrin III and haem respectively. The characterization of sirohaem decarboxylase is reported in molecular detail. Recombinant versions of D esulfovibrio desulfuricans , D esulfovibrio vulgaris and M ethanosarcina barkeri AhbA / B have been produced and their physical properties compared. The D . vulgaris and M . barkeri enzyme complexes both copurify with haem, whose redox state influences the activity of the latter. The kinetic parameters of the D . desulfuricans enzyme have been determined, the enzyme crystallized and its structure has been elucidated. The topology of the enzyme reveals that it shares a structural similarity to the AsnC / Lrp family of transcription factors. The active site is formed in the cavity between the two subunits and a AhbA / B ‐product complex with didecarboxysirohaem has been obtained. A mechanism for the decarboxylation of the kinetically stable carboxyl groups is proposed.