3TLZ

Microcin C7 self immunity protein MccF mutant W186F in complex with Adenosine Monophosphate

Summary for 3TLZ

• Entry DOI: 10.2210/pdb3tlz/pdb
• Related: 3TLA 3TLB 3TLC 3TLE 3TLG 3TLY
• Descriptor: MccF, ADENOSINE MONOPHOSPHATE, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: serine protease, hydrolase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 84453.95

Authors

Agarwal, V.,Nair, S.K. (deposition date: 2011-08-30, release date: 2012-02-29, Last modification date: 2023-09-13)

Primary citation

Agarwal, V.,Tikhonov, A.,Metlitskaya, A.,Severinov, K.,Nair, S.K.
Structure and function of a serine carboxypeptidase adapted for degradation of the protein synthesis antibiotic microcin C7.
Proc.Natl.Acad.Sci.USA, 109:4425-4430, 2012

PubMed Abstract: 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.

PubMed: 22388748
DOI: 10.1073/pnas.1114224109

Experimental method

X-RAY DIFFRACTION (1.5 Å)