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Crystal structure confirmation of JHP933 as a nucleotidyltransferase superfamily protein from Helicobacter pylori strain J99.

Zhao Y, Ye X, Su Y, Sun L, She F, Wu Y - PLoS ONE (2014)

Bottom Line: Studies suggested that certain genes in this region may play key roles in the pathogenesis of H. pylori-associated gastroduodenal diseases.A superposition demonstrates overall structural homology of the JHP933 N-terminal fragment with lincosamide antibiotic adenylyltransferase LinA and identifies a possible substrate-binding cleft of JHP933.Furthermore, through structural comparison with LinA and LinB, we pinpoint conservative active site residues which may contribute to divalent ion coordination and substrate binding.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian, China.

ABSTRACT
Helicobacter pylori is a well-known pathogen involved in the development of peptic ulcer, gastric adenocarcinoma and other forms of gastric cancer. Recently, there has been more considerable interest in strain-specific genes located in plasticity regions with great genetic variability. However, little is known about many of these genes. Studies suggested that certain genes in this region may play key roles in the pathogenesis of H. pylori-associated gastroduodenal diseases. JHP933, a conserved putative protein of unknown function, is encoded by the gene in plasticity region of H. pylori strain J99. Here we have determined the structure of JHP933. Our work demonstrates that JHP933 is a nucleotidyltransferase superfamily protein with a characteristic αβαβαβα topology. A superposition demonstrates overall structural homology of the JHP933 N-terminal fragment with lincosamide antibiotic adenylyltransferase LinA and identifies a possible substrate-binding cleft of JHP933. Furthermore, through structural comparison with LinA and LinB, we pinpoint conservative active site residues which may contribute to divalent ion coordination and substrate binding.

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Putative substrate binding site of JHP933.Ribbon diagram and surface representation of JHP933 are colored in lime, the modelled substrate lincomycin of the superimposed LinA/lincomycin complex is shown in ball-and-stick representation and colored in magenta (LinA protein not shown).
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pone-0104609-g004: Putative substrate binding site of JHP933.Ribbon diagram and surface representation of JHP933 are colored in lime, the modelled substrate lincomycin of the superimposed LinA/lincomycin complex is shown in ball-and-stick representation and colored in magenta (LinA protein not shown).

Mentions: A Dali search for structural homology identified lincosamide antibiotic adenylyltransferase LinA as the closest related structure with a Z-score of 9.6. LinA (pdb code: 4E8J) shares 16% sequence identity with JHP933 and superimposes with a Cα root-mean-square deviation (rmsd) of 2.7 Å over the N-terminal domain [Fig. 2 and 3]. The superposition of these two structures demonstrates a surprisingly high overall homology of the core structural elements including β-stands β1–β5 and the flanking α-helices α1–α4 in the N-terminal domain. The structural homology is highest in the core structure while significant differences can be seen in the addition of accessory structural elements and the loops which connect core elements [Fig. 2]. By comparison to the active site of LinA complex structure, a conservative large cleft is identified as a possible active site for substrate binding at the N-terminal core domain of JHP933. This substrate-binding cleft is surrounded mainly by β-strands β1, β2, β5 and α-helices α4, α2 with a size of around 13×20×20 Å [Fig. 4]. As LinA is a member of NTase superfamily, this high structural similarity further indicates that JHP933 should belong to the same superfamily.


Crystal structure confirmation of JHP933 as a nucleotidyltransferase superfamily protein from Helicobacter pylori strain J99.

Zhao Y, Ye X, Su Y, Sun L, She F, Wu Y - PLoS ONE (2014)

Putative substrate binding site of JHP933.Ribbon diagram and surface representation of JHP933 are colored in lime, the modelled substrate lincomycin of the superimposed LinA/lincomycin complex is shown in ball-and-stick representation and colored in magenta (LinA protein not shown).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4125220&req=5

pone-0104609-g004: Putative substrate binding site of JHP933.Ribbon diagram and surface representation of JHP933 are colored in lime, the modelled substrate lincomycin of the superimposed LinA/lincomycin complex is shown in ball-and-stick representation and colored in magenta (LinA protein not shown).
Mentions: A Dali search for structural homology identified lincosamide antibiotic adenylyltransferase LinA as the closest related structure with a Z-score of 9.6. LinA (pdb code: 4E8J) shares 16% sequence identity with JHP933 and superimposes with a Cα root-mean-square deviation (rmsd) of 2.7 Å over the N-terminal domain [Fig. 2 and 3]. The superposition of these two structures demonstrates a surprisingly high overall homology of the core structural elements including β-stands β1–β5 and the flanking α-helices α1–α4 in the N-terminal domain. The structural homology is highest in the core structure while significant differences can be seen in the addition of accessory structural elements and the loops which connect core elements [Fig. 2]. By comparison to the active site of LinA complex structure, a conservative large cleft is identified as a possible active site for substrate binding at the N-terminal core domain of JHP933. This substrate-binding cleft is surrounded mainly by β-strands β1, β2, β5 and α-helices α4, α2 with a size of around 13×20×20 Å [Fig. 4]. As LinA is a member of NTase superfamily, this high structural similarity further indicates that JHP933 should belong to the same superfamily.

Bottom Line: Studies suggested that certain genes in this region may play key roles in the pathogenesis of H. pylori-associated gastroduodenal diseases.A superposition demonstrates overall structural homology of the JHP933 N-terminal fragment with lincosamide antibiotic adenylyltransferase LinA and identifies a possible substrate-binding cleft of JHP933.Furthermore, through structural comparison with LinA and LinB, we pinpoint conservative active site residues which may contribute to divalent ion coordination and substrate binding.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian, China.

ABSTRACT
Helicobacter pylori is a well-known pathogen involved in the development of peptic ulcer, gastric adenocarcinoma and other forms of gastric cancer. Recently, there has been more considerable interest in strain-specific genes located in plasticity regions with great genetic variability. However, little is known about many of these genes. Studies suggested that certain genes in this region may play key roles in the pathogenesis of H. pylori-associated gastroduodenal diseases. JHP933, a conserved putative protein of unknown function, is encoded by the gene in plasticity region of H. pylori strain J99. Here we have determined the structure of JHP933. Our work demonstrates that JHP933 is a nucleotidyltransferase superfamily protein with a characteristic αβαβαβα topology. A superposition demonstrates overall structural homology of the JHP933 N-terminal fragment with lincosamide antibiotic adenylyltransferase LinA and identifies a possible substrate-binding cleft of JHP933. Furthermore, through structural comparison with LinA and LinB, we pinpoint conservative active site residues which may contribute to divalent ion coordination and substrate binding.

Show MeSH
Related in: MedlinePlus