title: Crystal structure of AibC, a reductase involved in alternative de novo isovaleryl coenzyme A biosynthesis in Myxococcus xanthus.
abstract: Isovaleryl coenzyme A (IV-CoA) performs a crucial role during development and fruiting-body formation in myxobacteria, which is reflected in the existence of a de novo biosynthetic pathway that is highly upregulated when leucine, the common precursor of IV-CoA, is limited. The final step in de novo IV-CoA biosynthesis is catalyzed by AibC, a medium-chain dehydrogenase/reductase. Here, the crystal structure of AibC from Myxococcus xanthus refined to 2.55 Å resolution is presented. The protein adopts two different conformations in the crystal lattice, which is a consequence of partial interaction with the purification tag. Based on this structure, it is suggested that AibC most probably uses a Zn(2+)-supported catalytic mechanism in which NADPH is preferred over NADH. Taken together, this study reveals structural details of the alternative IV-CoA-producing pathway in myxobacteria, which may serve as a base for further biotechnological research and biofuel production.
authors.affiliation: Structure and Function of Proteins, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Bock
authors.affiliation: Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland, Saarland University, Universitätscampus E8 1, 66123 Saarbrücken, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Müller
authors.affiliation: Structure and Function of Proteins, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
authors.forename: Wulf
authors.initials: W
authors.lastname: Blankenfeldt
mesh_terms: D000214:Acyl Coenzyme A / Q000096:biosynthesis / Q000737:chemistry*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002413:Cations, Divalent; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D050769:Isovaleryl-CoA Dehydrogenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D016941:Myxococcus xanthus / Q000737:chemistry* / Q000201:enzymology; D009249:NADP / Q000737:chemistry* / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000214:Acyl Coenzyme A; D001426:Bacterial Proteins; D002413:Cations, Divalent; D011993:Recombinant Fusion Proteins; D009249:NADP; C017447:isovaleryl-coenzyme A; D050769:Isovaleryl-CoA Dehydrogenase; D015032:Zinc
keywords: Myxococcus xanthus; TEV protease-recognition sequence; alternative isovaleryl coenzyme A biosynthesis; hexahistidine tag; medium-chain dehydrogenase/reductase; zinc-dependence