title: The structure of Mlc titration factor A (MtfA/YeeI) reveals a prototypical zinc metallopeptidase related to anthrax lethal factor.
abstract: 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 Å, respectively. MtfA contains a conserved H(149)E(150)XXH(153)+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).
authors.affiliation: Joint Center for Structural Genomics, SLAC National Accelerator Laboratory, Menlo Park, CA, USA.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Xu
authors.forename: Anna-Katharina
authors.initials: AK
authors.lastname: Göhler
authors.forename: Anne
authors.initials: A
authors.lastname: Kosfeld
authors.forename: Dennis
authors.initials: D
authors.lastname: Carlton
authors.forename: Hsiu-Ju
authors.initials: HJ
authors.lastname: Chiu
authors.forename: Heath E
authors.initials: HE
authors.lastname: Klock
authors.forename: Mark W
authors.initials: MW
authors.lastname: Knuth
authors.forename: Mitchell D
authors.initials: MD
authors.lastname: Miller
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Elsliger
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Deacon
authors.forename: Adam
authors.initials: A
authors.lastname: Godzik
authors.forename: Scott A
authors.initials: SA
authors.lastname: Lesley
authors.forename: Knut
authors.initials: K
authors.lastname: Jahreis
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001427:Bacterial Toxins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D007711:Klebsiella pneumoniae / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D008666:Metalloendopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D045726:Metalloproteases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D016415:Sequence Alignment; D015032:Zinc / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C030325:anthrax toxin; D045726:Metalloproteases; D008666:Metalloendopeptidases; C470925:Mop protein, Vibrio cholerae; D015032:Zinc