3tlc | pdb_00003tlc

Microcin C7 self immunity protein MccF in complex with Microcin C7 antibiotic

spinqualitylabelsall models 3tlc, resolution 1.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3tlc is a 2 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.3Å Ligands: 7MD, EDO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MCCF_ECOLX Involved in specific self-immunity to microcin C7. Publication Abstract from PubMed Several classes of naturally occurring antimicrobials exert their antibiotic activity by specifically targeting aminoacyl-tRNA synthetases, validating these enzymes as drug targets. The aspartyl tRNA synthetase "Trojan horse" inhibitor microcin C7 (McC7) consists of a nonhydrolyzable aspartyl-adenylate conjugated to a hexapeptide carrier that facilitates active import into bacterial cells through an oligopeptide transport system. Subsequent proteolytic processing releases the toxic compound inside the cell. Producing strains of McC7 must protect themselves against autotoxicity that may result from premature processing. The mccF gene confers resistance against endogenous and exogenous McC7 by hydrolyzing the amide bond that connects the peptide and nucleotide moieties of McC7. We present here crystal structures of MccF, in complex with various ligands. The MccF structure is similar to that of dipeptide ld-carboxypeptidase, but with an additional loop proximal to the active site that serves as the primary determinant for recognition of adenylated substrates. Wild-type MccF only hydrolyzes the naturally occurring aspartyl phosphoramidate McC7 and synthetic peptidyl sulfamoyl adenylates that contain anionic side chains. We show that substitutions of two active site MccF residues result in a specificity switch toward aromatic aminoacyl-adenylate substrates. These results suggest how MccF-like enzymes may be used to avert various toxic aminoacyl-adenylates that accumulate during antibiotic biosynthesis or in normal metabolism of the cell. Structure and function of a serine carboxypeptidase adapted for degradation of the protein synthesis antibiotic microcin C7.,Agarwal V, Tikhonov A, Metlitskaya A, Severinov K, Nair SK Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):4425-30. Epub 2012 Mar 2. PMID:22388748 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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