title: The Cell Shape-determining Csd6 Protein from Helicobacter pylori Constitutes a New Family of L,D-Carboxypeptidase.
abstract: Helicobacter pylori causes gastrointestinal diseases, including gastric cancer. Its high motility in the viscous gastric mucosa facilitates colonization of the human stomach and depends on the helical cell shape and the flagella. In H. pylori, Csd6 is one of the cell shape-determining proteins that play key roles in alteration of cross-linking or by trimming of peptidoglycan muropeptides. Csd6 is also involved in deglycosylation of the flagellar protein FlaA. To better understand its function, biochemical, biophysical, and structural characterizations were carried out. We show that Csd6 has a three-domain architecture and exists as a dimer in solution. The N-terminal domain plays a key role in dimerization. The middle catalytic domain resembles those of l,d-transpeptidases, but its pocket-shaped active site is uniquely defined by the four loops I to IV, among which loops I and III show the most distinct variations from the known l,d-transpeptidases. Mass analyses confirm that Csd6 functions only as an l,d-carboxypeptidase and not as an l,d-transpeptidase. The d-Ala-complexed structure suggests possible binding modes of both the substrate and product to the catalytic domain. The C-terminal nuclear transport factor 2-like domain possesses a deep pocket for possible binding of pseudaminic acid, and in silico docking supports its role in deglycosylation of flagellin. On the basis of these findings, it is proposed that H. pylori Csd6 and its homologs constitute a new family of l,d-carboxypeptidase. This work provides insights into the function of Csd6 in regulating the helical cell shape and motility of H. pylori.
authors: From the Departments of Chemistry and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Hyoun Sook
authors: HS
authors: Kim
authors: Biophysics and Chemical Biology, College of Natural Sciences, and.
authors: Ha Na
authors: HN
authors: Im
authors: Biophysics and Chemical Biology, College of Natural Sciences, and.
authors: Doo Ri
authors: DR
authors: An
authors: Biophysics and Chemical Biology, College of Natural Sciences, and.
authors: Ji Young
authors: JY
authors: Yoon
authors: From the Departments of Chemistry and.
authors: Jun Young
authors: JY
authors: Jang
authors: the Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556.
authors: Shahriar
authors: S
authors: Mobashery
authors: the Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556.
authors: Dusan
authors: D
authors: Hesek
authors: the Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556.
authors: Mijoon
authors: M
authors: Lee
authors: the National Leading Research Laboratory of Molecular Modeling and Drug Design, College of Pharmacy, Graduate School of Pharmaceutical Sciences, and Global Top 5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors: Jakyung
authors: J
authors: Yoo
authors: the National Leading Research Laboratory of Molecular Modeling and Drug Design, College of Pharmacy, Graduate School of Pharmaceutical Sciences, and Global Top 5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors: Minghua
authors: M
authors: Cui
authors: the National Leading Research Laboratory of Molecular Modeling and Drug Design, College of Pharmacy, Graduate School of Pharmaceutical Sciences, and Global Top 5 Research Program, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors: Sun
authors: S
authors: Choi
authors: the Department of Physics, POSTECH, Pohang 790-784, Republic of Korea.
authors: Cheolhee
authors: C
authors: Kim
authors: the Department of Physics, POSTECH, Pohang 790-784, Republic of Korea.
authors: Nam Ki
authors: NK
authors: Lee
authors: the Department of Chemistry, Mokpo National University, Chonnam 534-729, Republic of Korea.
authors: Soon-Jong
authors: SJ
authors: Kim
authors: the Division of Mass Spectrometry, Korea Basic Science Institute, Chungbuk 363-883, Republic of Korea, and.
authors: Jin Young
authors: JY
authors: Kim
authors: the Division of Mass Spectrometry, Korea Basic Science Institute, Chungbuk 363-883, Republic of Korea, and.
authors: Geul
authors: G
authors: Bang
authors: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Byung Woo
authors: BW
authors: Han
authors: the Biomolecular Function Research Branch, Division of Convergence Technology, Research Institute, National Cancer Center, Gyeonggi 410-769, Republic of Korea.
authors: Byung Il
authors: BI
authors: Lee
authors: From the Departments of Chemistry and yoonhj@snu.ac.kr.
authors: Hye Jin
authors: HJ
authors: Yoon
authors: From the Departments of Chemistry and Biophysics and Chemical Biology, College of Natural Sciences, and sewonsuh@snu.ac.kr.
authors: Se Won
authors: SW
authors: Suh
mesh_terms: D000595:Amino Acid Sequence; D002268:Carboxypeptidases / Q000737:chemistry / Q000378:metabolism*; D020134:Catalytic Domain; D048430:Cell Shape; D016480:Helicobacter pylori / Q000166:cytology* / Q000201:enzymology*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D013400:Sugar Acids / Q000378:metabolism
chemical_list: C513444:5,7-diacetamido-3,5,7,9-tetradeoxynonulosonic acid; D013400:Sugar Acids; D002268:Carboxypeptidases
keywords: Csd6; HP0518; Helicobacter pylori; L,D-carboxypeptidase; cell motility; cell shape; flagellin; peptidoglycan; protein structure; structure-function