title: Homology modeling, molecular docking and DNA binding studies of nucleotide excision repair UvrC protein from M. tuberculosis.
abstract: Mycobacterium tuberculosis is a Gram positive, acid-fast bacteria belonging to genus Mycobacterium, is the leading causative agent of most cases of tuberculosis. The pathogenicity of the bacteria is enhanced by its developed DNA repair mechanism which consists of machineries such as nucleotide excision repair. Nucleotide excision repair consists of excinuclease protein UvrABC endonuclease, multi-enzymatic complex which carries out repair of damaged DNA in sequential manner. UvrC protein is a part of this complex and thus helps to repair the damaged DNA of M. tuberculosis. Hence, structural bioinformatics study of UvrC protein from M. tuberculosis was carried out using homology modeling and molecular docking techniques. Assessment of the reliability of the homology model was carried out by predicting its secondary structure along with its model validation. The predicted structure was docked with the ATP and the interacting amino acid residues of UvrC protein with the ATP were found to be TRP539, PHE89, GLU536, ILE402 and ARG575. The binding of UvrC protein with the DNA showed two different domains. The residues from domain I of the protein VAL526, THR524 and LEU521 interact with the DNA whereas, amino acids interacting from the domain II of the UvrC protein included ARG597, GLU595, GLY594 and GLY592 residues. This predicted model could be useful to design new inhibitors of UvrC enzyme to prevent pathogenesis of Mycobacterium and so the tuberculosis.
authors: Structural Bioinformatics Unit, Department of Biochemistry, Shivaji University, Kolhapur, 416 004, Maharashtra, India.
authors: Rishikesh S
authors: RS
authors: Parulekar
authors: Sagar H
authors: SH
authors: Barage
authors: Chidambar B
authors: CB
authors: Jalkute
authors: Maruti J
authors: MJ
authors: Dhanavade
authors: Prayagraj M
authors: PM
authors: Fandilolu
authors: Kailas D
authors: KD
authors: Sonawane
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004260:DNA Repair; D004706:Endodeoxyribonucleases / Q000737:chemistry / Q000378:metabolism*; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D011485:Protein Binding; D011487:Protein Conformation; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein
chemical_list: D001426:Bacterial Proteins; D004247:DNA; D004706:Endodeoxyribonucleases
references: J Biol Chem. 2001 Feb 9;276(6):3904-10
references: 11056168
references: Proc Natl Acad Sci U S A. 1997 May 13;94(10):5243-8
references: 9144222
references: FEMS Microbiol Rev. 2009 May;33(3):471-87
references: 19385996
references: Curr Drug Targets. 2010 Mar;11(3):261-3
references: 20214598
references: Proc Natl Acad Sci U S A. 1985 Aug;82(15):4925-9
references: 3161077
references: J Bacteriol. 2007 Mar;189(5):1542-55
references: 17158674
references: J Cheminform. 2011 Oct 07;3:33
references: 21982300
references: J Biol Chem. 1992 Sep 5;267(25):17693-700
references: 1387640
references: J Biol Chem. 2004 Dec 3;279(49):51574-80
references: 15456749
references: Protein J. 2013 Jun;32(5):356-64
references: 23660814
references: Bioinformatics. 2011 Feb 1;27(3):343-50
references: 21134891
references: J Biol Chem. 2000 Mar 17;275(11):8044-50
references: 10713125
references: Curr Drug Targets. 2008 Dec;9(12):1048-53
references: 19128214
references: Genetics. 1966 Jun;53(6):1119-36
references: 5335128
references: J Biol Chem. 2002 Jan 11;277(2):1553-9
references: 11687584
references: Infect Immun. 2005 Aug;73(8):4581-7
references: 16040969
references: J Comput Chem. 2004 Oct;25(13):1605-12
references: 15264254
references: Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):8841-8
references: 10922044
references: Acta Crystallogr D Biol Crystallogr. 1999 Mar;55(Pt 3):704-5
references: 10089476
references: J Mol Biol. 1999 Sep 17;292(2):195-202
references: 10493868
references: J Mol Biol. 1993 Dec 5;234(3):779-815
references: 8254673
references: Bioinformatics. 2007 Jul 1;23(13):1694-6
references: 17459960
references: Nucleic Acids Res. 2011 Sep 1;39(16):7316-28
references: 21622956
references: EMBO J. 2002 Aug 1;21(15):4196-205
references: 12145219
references: Curr Drug Targets. 2008 Dec;9(12):1040-7
references: 19128213
references: Trends Biochem Sci. 1995 Sep;20(9):374
references: 7482707
references: Tuber Lung Dis. 1997;78(5-6):247-55
references: 10209679
references: Clin Exp Immunol. 2000 Aug;121(2):302-10
references: 10931146
references: Proteins. 2003 Feb 15;50(3):437-50
references: 12557186
references: J Biol Chem. 1990 Sep 15;265(26):15796-803
references: 2168423
references: J Mol Graph. 1990 Mar;8(1):52-6, 29
references: 2268628
references: Proc Natl Acad Sci U S A. 1985 Oct;82(20):6774-8
references: 2931721
references: Clin Microbiol Rev. 2006 Jul;19(3):558-70
references: 16847086
references: Curr Drug Targets. 2010 Mar;11(3):327-34
references: 20210757
references: Biophys J. 2007 May 15;92(10):3524-40
references: 17293393
references: J Biol Chem. 1996 Apr 19;271(16):9612-8
references: 8621636
references: Nat Struct Mol Biol. 2006 Apr;13(4):360-4
references: 16532007
references: Nucleic Acids Res. 2012 Sep 1;40(17):8743-58
references: 22753105
references: J Biol Chem. 1995 Apr 7;270(14):8319-27
references: 7713940
references: J Biol Chem. 1992 Sep 5;267(25):17688-92
references: 1387639
references: EMBO J. 2001 Feb 1;20(3):601-11
references: 11157766
references: Curr Med Chem. 2011;18(9):1339-52
references: 21366530
references: J Biochem. 1999 Dec;126(6):986-90
references: 10578047
references: Cell. 1983 May;33(1):249-60
references: 6380755
references: J Biol Chem. 2000 Feb 18;275(7):5120-3
references: 10671556
references: Nucleic Acids Res. 1997 Dec 15;25(24):4876-82
references: 9396791
references: Mutat Res. 2000 Aug 30;460(3-4):277-300
references: 10946234
references: J Mol Biol. 1990 Oct 5;215(3):403-10
references: 2231712