Molecular interactions of UvrB protein and DNA from Helicobacter pylori: Insight into a molecular modeling approach.
Helicobacter pylori (H. pylori) persevere in the human stomach, an environment in which they encounter many DNA-damaging conditions, including gastric acidity. The pathogenicity of H. pylori is enhanced by its well-developed DNA repair mechanism, thought of as 'machinery,' such as nucleotide excision repair (NER). NER involves multi-enzymatic excinuclease proteins (UvrABC endonuclease), which repair damaged DNA in a sequential manner. UvrB is the central component in prokaryotic NER, essential for damage recognition. Therefore, molecular modeling studies of UvrB protein from H. pylori are carried out with homology modeling and molecular dynamics (MD) simulations. The results reveal that the predicted structure is bound to a DNA hairpin with 3-bp stem, an 11-nucleotide loop, and 3-nt 3' overhang. In addition, a mutation of the Y96A variant indicates reduction in the binding affinity for DNA. Free-energy calculations demonstrate the stability of the complex and help identify key residues in various interactions based on residue decomposition analysis. Stability comparative studies between wild type and mutant protein-DNA complexes indicate that the former is relatively more stable than the mutant form. This predicted model could also be useful in designing new inhibitors for UvrB protein, as well as preventing the pathogenesis of H. pylori.
Division of Applied Life Science (BK21 Plus), Systems and Synthetic Agrobiotech Center (SSAC), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), 501 Jinju-daero, Jinju 52828, Republic of Korea.
Rohit
R
Bavi
Division of Applied Life Science (BK21 Plus), Systems and Synthetic Agrobiotech Center (SSAC), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), 501 Jinju-daero, Jinju 52828, Republic of Korea.
Raj
R
Kumar
Division of Applied Life Science (BK21 Plus), Systems and Synthetic Agrobiotech Center (SSAC), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), 501 Jinju-daero, Jinju 52828, Republic of Korea.
Shailima
S
Rampogu
Division of Applied Life Science (BK21 Plus), Systems and Synthetic Agrobiotech Center (SSAC), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), 501 Jinju-daero, Jinju 52828, Republic of Korea.
Minky
M
Son
Division of Applied Life Science (BK21 Plus), Systems and Synthetic Agrobiotech Center (SSAC), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), 501 Jinju-daero, Jinju 52828, Republic of Korea.
Chanin
C
Park
Division of Applied Life Science (BK21 Plus), Systems and Synthetic Agrobiotech Center (SSAC), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), 501 Jinju-daero, Jinju 52828, Republic of Korea.
Ayoung
A
Baek
Division of Quality of Life, Korea Research Institute of Standards and Science, Daejeon 305-340, Republic of Korea.
Hyong-Ha
HH
Kim
Bio Computing Major, Korean German Institute of Technology, Seoul 157-033, Republic of Korea.
Jung-Keun
JK
Suh
Department of Internal Medicine, College of Medicine, Busan Paik Hospital, Inje University, Republic of Korea. Electronic address: psjgenesis@hanmail.net.
Seok Ju
SJ
Park
Division of Applied Life Science (BK21 Plus), Systems and Synthetic Agrobiotech Center (SSAC), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), 501 Jinju-daero, Jinju 52828, Republic of Korea. Electronic address: kwlee@gnu.ac.kr.
Keun Woo
KW
Lee
D019943:Amino Acid Substitution; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004269:DNA, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016480:Helicobacter pylori / Q000201:enzymology* / Q000235:genetics; D008958:Models, Molecular; D020125:Mutation, Missense
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004265:DNA Helicases
Free energy calculations; Helicobacter pylori; Homology modeling and molecular dynamics simulations; Nucleotide excision repair; UvrB