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Biochem Biophys Res Commun. 2016 Jun 3;474(3):522-527. doi: 10.1016/j.bbrc.2016.04.126. Epub 2016 Apr 24.

Structural and biochemical characterization of the Bacillus cereus 3-hydroxyisobutyrate dehydrogenase.

Author information

1
Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
2
Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
3
College of Veterinary Medicine, Kangwon National University, Chuncheon 24341, Republic of Korea.
4
Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea.
5
Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea; Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 24341, Republic of Korea. Electronic address: sungil@kangwon.ac.kr.

Abstract

The 3-hydroxyisobutyrate dehydrogenase (HIBADH) family catalyzes the NAD(+)- or NADP(+)-dependent oxidation of various β-hydroxyacid substrates into their cognate semialdehydes for diverse metabolic pathways. Because HIBADH group members exhibit different substrate specificities, the substrate-recognition mode of each enzyme should be individually characterized. In the current study, we report the biochemical and structural analysis of a HIBADH group enzyme from Bacillus cereus (bcHIBADH). bcHIBADH mediates a dehydrogenation reaction on S-3-hydroxyisobutyrate substrate with high catalytic efficiency in an NAD(+)-dependent manner; it also oxidizes l-serine and 3-hydroxypropionate with lower activity. bcHIBADH consists of two domains and is further assembled into a functional dimer rather than a tetramer that has been commonly observed in other prokaryotic HIBADH group members. In the bcHIBADH structure, the interdomain cleft forms a putative active site and simultaneously accommodates both an NAD(+) cofactor and a substrate mimic. Our structure-based comparative analysis highlights structural motifs that are important in the cofactor and substrate recognition of the HIBADH group.

KEYWORDS:

3-hydroxyisobutyrate dehydrogenase; Bacillus cereus; Crystal structure; Substrate; β-hydroxyacid dehydrogenase

PMID:
27120461
DOI:
10.1016/j.bbrc.2016.04.126
[Indexed for MEDLINE]

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