期刊
BIOCHEMISTRY
卷 52, 期 38, 页码 6662-6671出版社
AMER CHEMICAL SOC
DOI: 10.1021/bi400845b
关键词
-
资金
- National Institutes of Health [GM40466, GM40466-S1, GM100943, GM66569]
- Graduate Traineeship [GM008700]
A family of dinuclear iron cluster-containing oxygenases that catalyze beta-hydroxylation tailoring reactions in natural product biosynthesis by nonribosomal peptide synthetase (NRPS) systems was recently described [Makris, T. M., Chakrabarti, M., Mfinck, E., and Lipscomb, J. D. (2010) Proc. Natl. Acad. Sci. U.S.A. 107, 15391-15396]. Here, the 2.17 A X-ray crystal structure of the archetypal enzyme from the family, Cm1A, is reported. Cm1A catalyzes /3-hydroxylation of L-paminophenylalanine during chloramphenicol biosynthesis. The fold of the N-terminal domain of Cm1A is unlike any previously reported, but the C-terminal domain has the afifia fold of the metallo-beta-lactamase (MBL) superfamily. The diiron cluster bound in the C-terminal domain is coordinated by an acetate, three His residues, two Asp residues, one Glu residue, and a bridging oxo moiety. One of the Asp ligands forms an unusual monodentate bridge. No other oxygen-activating diiron enzyme utilizes this ligation or the MBL protein fold. The N-terminal domain facilitates dimerization, but using computational docking and a sequence-based structural comparison to homologues, we hypothesize that it likely serves additional roles in NRPS recognition and the regulation of 02 activation.
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