4JO0

Crystal Structure of CmlA, a diiron beta-hydroxylase from Streptomyces venezuelae

Summary for 4JO0

• Entry DOI: 10.2210/pdb4jo0/pdb
• Descriptor: CmlA, FE (III) ION, OXYGEN ATOM, ... (7 entities in total)
• Functional Keywords: nonheme oxygenase, dinuclear iron cluster, antibiotic, beta-hydroxylation, oxidoreductase
• Biological source: Streptomyces venezuelae
• Total number of polymer chains: 1
• Total formula weight: 60918.01

Authors

Knoot, C.J.,Makris, T.M.,Wilmot, C.M.,Lipscomb, J.D. (deposition date: 2013-03-16, release date: 2013-09-11, Last modification date: 2024-02-28)

Primary citation

Makris, T.M.,Knoot, C.J.,Wilmot, C.M.,Lipscomb, J.D.
Structure of a Dinuclear Iron Cluster-Containing beta-Hydroxylase Active in Antibiotic Biosynthesis.
Biochemistry, 52:6662-6671, 2013

PubMed Abstract: A family of dinuclear iron cluster-containing oxygenases that catalyze β-hydroxylation tailoring reactions in natural product biosynthesis by nonribosomal peptide synthetase (NRPS) systems was recently described [Makris, T. M., Chakrabarti, M., Münck, E., and Lipscomb, J. D. (2010) Proc. Natl. Acad. Sci. U.S.A. 107, 15391-15396]. Here, the 2.17 Å X-ray crystal structure of the archetypal enzyme from the family, CmlA, is reported. CmlA catalyzes β-hydroxylation of l-p-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 αββα fold of the metallo-β-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 O2 activation.

PubMed: 23980641
DOI: 10.1021/bi400845b

Experimental method

X-RAY DIFFRACTION (2.17 Å)