Chauviac, Francois-Xavier and Bommer, M. and Yan, Jun and Parkin, G. and Daviter, Tina and Lowden, Philip A.S. and Raven, E. L. and Thalassinos, Konstantinos and Keep, Nicholas H. (2012) Crystal structure of reduced MsAcg a putative nitroreductase from Mycobacterium smegmatis, and a close homologue of Mycobacterium tuberculosis Acg. Journal of Biological Chemistry 287 , pp. 44372-44383. ISSN 0021-9258.
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Abstract
This paper presents the structure of MsAcg (MSMEG_5246), a Mycobacterium smegmatis homologue of M.tuberculosis Acg (Rv2032) in its reduced form at 1.6 Å resolution using X-ray crystallography. Rv2032 is one of the most induced genes under the hypoxic model of tuberculosis dormancy. The Acg family turn out to be unusual flavin mononucleotide (FMN) binding proteins that have probably arisen by gene duplication and fusion from a classical homodimeric nitroreductase, such that the monomeric protein resembles a classical nitroreductase dimer, but with one active site deleted and the other active site covered by a unique lid. The FMN cofactor is not reduced by either NADH or NADPH, but the chemically reduced enzyme is capable of reduction of nitro substrates, albeit at no kinetic advantage over free FMN. The reduced enzyme is rapidly oxidised by oxygen, but without any evidence for a radical state commonly seen in oxygen sensitive nitroreductases. The presence of the unique lid domain, the lack of reduction by NAD(P)H and the slow rate of reaction of the chemically reduced protein raises a possible alternative function of Acg proteins in FMN storage or sequestration from other biochemical pathways, as part of the bacteria's adaptation to a dormancy state.
Metadata
| Item Type: | Article |
|---|---|
| Keyword(s) / Subject(s): | Enzyme structure, Flavin, Mycobacteria, Mycobacterium tuberculosis, Protein evolution, Protein structure, X-ray crystallography |
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Research Centres and Institutes: | Structural Molecular Biology, Institute of (ISMB) |
| Depositing User: | Administrator |
| Date Deposited: | 14 Nov 2012 09:36 |
| Last Modified: | 02 Aug 2023 17:00 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/5690 |
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