4jo0 | pdb_00004jo0
Crystal Structure of CmlA, a diiron beta-hydroxylase from Streptomyces venezuelae
Structural highlights
FunctionCMLA_STRVP Involved in chloramphenicol biosynthesis (PubMed:20713732). Catalyzes the beta-hydroxylation of 4-amino-L-phenylalanine (L-PAPA) covalently bound to CmlP to form L-p-aminophenylserine (PubMed:20713732).[1] Publication Abstract from PubMedA family of dinuclear iron cluster-containing oxygenases was recently described that catalyze beta-hydroxylation tailoring reactions in natural product biosynthesis by nonribosomal peptide synthetase (NRPS) systems (Makris, T. M., Chakrabarti, M., Munck, E., and Lipscomb, J. D. (2010) <i>Proc. Natl. Acad. Sci. U.S.A. 107</i>, 15391-15396). Here, the 2.17 A X-ray crystal structure of the archetypal enzyme from the family, CmlA, is reported. CmlA catalyzes beta-hydroxylation of L-<i>p</i>-aminophenylalanine during chloramphenicol biosynthesis. The fold of the N-terminal domain of CmlA is unlike any previously reported, but the C-terminal domain has the alphabetabetaalpha-fold of the metallo-beta-lactamase (MBL) superfamily. The diiron cluster bound in the C-terminal domain is coordinated by an acetate, three His, two Asp, one Glu 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 homologs, we hypothesize that it likely serves additional roles in NRPS recognition and the regulation of O<sub>2</sub activation. Structure of a dinuclear iron cluster-containing beta hydroxylase active in antibiotic biosynthesis.,Makris TM, Knoot CJ, Wilmot CM, Lipscomb JD Biochemistry. 2013 Aug 27. PMID:23980641[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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