S-Space College of Natural Sciences (자연과학대학) Biophysics and Chemical Biology (생물물리 및 화학생물학과) Theses (Ph.D. / Sc.D._생물물리 및 화학생물학과)
Structural Studies of Csd6 Protein from Helicobacter pylori and Rv2258c Protein from Mycobacterium tuberculosis
- 자연과학대학 생물물리 및 화학생물학과
- Issue Date
- 서울대학교 대학원
- Csd6 / cell shape / L; D-carboxypeptidase / Helicobacter pylori / HP0518 / flagellin / peptidoglycan / cell motility / protein structure / structure-function / Rv2258c / Mycobacterium tuberculosis / small-molecule methyltransferase / sinefungin / S-adenosyl-L-homocysteine
- 학위논문 (박사)-- 서울대학교 대학원 : 화학생물학과, 2016. 8. 서세원.
- Helicobacter pylori causes gastrointestinal diseases, including gastric cancer. Mycobacterium tuberculosis induces tuberculosis, claiming the lives of millions of people in the world every year. Increasing drug-resistance among bacterial pathogens is a serious global health issue. Therefore, discovery of new antimicrobial agents is needed urgently. Identifying the molecular and biological functions of proteins from pathogenic bacteria would provide the groundwork for the development of new antibacterial drug targets. In this study, I have determined the crystal structures of Csd6 from H. pylori and Rv2258c from M. tuberculosis.
The H. pylori Csd6 protein plays a key role in determining the helical cell shape by trimming of peptidoglycan muropeptides. Csd6 is also involved in deglycosylation of the flagellar protein FlaA. The structure of Csd6 reveals that its middle catalytic domain resembles those of L,D-transpeptidases but its pocket-shaped active-site shows distinct variations from the known L,D-transpeptidases. Mass analyses confirm that Csd6 functions only as an L,D-carboxypeptidase but not as an L,D-transpeptidase. D-Ala-complexed structure of Csd6 reveals binding modes of both the substrate and product to the catalytic domain. On the basis of structure-function analysis, Csd6 and its homologs are proposed to constitute a new family of L,D-carboxypeptidase.
The M. tuberculosis Rv2258c protein is predicted to be an S-adenosyl-L-methionine-dependent methyltransferase (MTase). MTases mediate a wide variety of cellular processes, such as cell signaling, metabolite synthesis, and gene regulation in nearly all living organisms. The structure of Rv2258c shows that its monomer consists of two domains linked by a long α-helix. The N-terminal domain is essential for dimerization and the C-terminal catalytic domain has the Class I MTase fold. The overall fold of Rv2258c, as well as its interactions with bound sinefungin (or S-adenosyl-L-homocysteine), are similar to small-molecule MTases. Rv2258c has a relatively large hydrophobic cavity for binding the methyl-accepting substrate, suggesting that bulky nonpolar molecules might be targeted for methylation by Rv2258c in M. tuberculosis.