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

Author:

Xu Qingping12,Göhler Anna-Katharina3,Kosfeld Anne3,Carlton Dennis14,Chiu Hsiu-Ju12,Klock Heath E.15,Knuth Mark W.15,Miller Mitchell D.12,Elsliger Marc-André14,Deacon Ashley M.12,Godzik Adam167,Lesley Scott A.145,Jahreis Knut3,Wilson Ian A.14

Affiliation:

1. Joint Center for Structural Genomics, SLAC National Accelerator Laboratory, Menlo Park, California, USA

2. Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, California, USA

3. Department of Biology and Chemistry, University of Osnabrück, Osnabrück, Germany

4. Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA

5. Protein Sciences Department, Genomics Institute of the Novartis Research Foundation, San Diego, California, USA

6. Program on Bioinformatics and Systems Biology, Sanford-Burnham Medical Research Institute, La Jolla, California, USA

7. Center for Research in Biological Systems, University of California, San Diego, La Jolla, California, USA

Abstract

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).

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3