The Structure of Mlc Titration Factor A (MtfA/YeeI) Reveals a Prototypical Zinc Metallopeptidase Related to Anthrax Lethal Factor

Autor(en): Xu, Qingping
Goehler, Anna-Katharina
Kosfeld, Anne
Carlton, Dennis
Chiu, Hsiu-Ju
Klock, Heath E.
Knuth, Mark W.
Miller, Mitchell D.
Elsliger, Marc-Andre
Deacon, Ashley M.
Godzik, Adam
Lesley, Scott A.
Jahreis, Knut
Wilson, Ian A.
Stichwörter: BACILLUS-ANTHRACIS; CRYSTAL-STRUCTURE; EPIDEMIC VIBRIO-CHOLERAE; ESCHERICHIA-COLI K-12; GLUCOSE-PHOSPHOTRANSFERASE SYSTEM; HIGH-PATHOGENICITY ISLAND; MEMBRANE SEQUESTRATION; Microbiology; PROTEIN; SECONDARY STRUCTURE; STRUCTURE PREDICTION
Erscheinungsdatum: 2012
Herausgeber: AMER SOC MICROBIOLOGY
Journal: JOURNAL OF BACTERIOLOGY
Volumen: 194
Ausgabe: 11
Startseite: 2987
Seitenende: 2999
Zusammenfassung: 
MtfA of Escherichia coli (formerly YeeI) was previously identified as a regulator of the phosphoenolpyruvate (PEP)-dependent: glucose phosphotransferase system. MtfA homolog proteins are highly conserved, especially among beta- and gammaproteobacteria. We determined the crystal structures of the full-length MtfA apoenzyme from Klebsiella pneumoniae and its complex with zinc (holoenzyme) at 2.2 and 1.95 angstrom, respectively. MtfA contains a conserved (HEXXH153)-E-149-X-150+E-212+Y-205 metallopeptidase motif. The presence of zinc in the active site induces significant conformational changes in the region around Tyr205 compared to the conformation of the apoenzyme. Additionally, the zinc-bound MtfA structure is in a self-inhibitory conformation where a region that was disordered in the unliganded structure is now observed in the active site and a nonproductive state of the enzyme is formed. MtfA is related to the catalytic domain of the anthrax lethal factor and the Mop protein involved in the virulence of Vibrio cholerae, with conservation in both overall structure and in the residues around the active site. These results clearly provide support for MtfA as a prototypical zinc metallopeptidase (gluzincin clan).
ISSN: 00219193
DOI: 10.1128/JB.00038-12

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