title: Molecular modeling and molecular dynamics simulations of recombinase Rad51.
abstract: The Rad51 ATPase plays central roles in DNA homologous recombination. Yeast Rad51 dimer structure in the active form of the filament was constructed using homology modeling techniques, and all-atom molecular dynamics (MD) simulations were performed using the modeled structure. We found two crucial interaction networks involving ATP: one is among the γ-phosphate of ATP, K(+) ions, H352, and D374; the other is among the adenine ring of ATP, R228, and P379. Multiple MD simulations were performed in which the number of bound K(+) ions was changed. The simulated structures suggested that K(+) ions are indispensable for the stabilization of the active dimer and resemble the arginine and lysine fingers of other P-loop containing ATPases and GTPases. MD simulations also showed that the adenine ring of ATP mediates interactions between adjacent protomers. Furthermore, in MD simulations starting from a structure just after ATP hydrolysis, the opening motion corresponding to dissociation from DNA was observed. These results support the hypothesis that ATP and K(+) ions function as glue between protomers.
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, Yokohama, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kokabu
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Ikeguchi
mesh_terms: D000225:Adenine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D056004:Molecular Dynamics Simulation; D011188:Potassium / Q000378:metabolism; D055503:Protein Multimerization; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D051135:Rad51 Recombinase / Q000737:chemistry* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015003:Yeasts / Q000201:enzymology
chemical_list: D000255:Adenosine Triphosphate; D051135:Rad51 Recombinase; D000225:Adenine; D011188:Potassium
references.citation: J Biol Chem. 2011 Dec 16;286(50):43569-76
references.pmid: 22033972
references.citation: J Comput Chem. 2004 Mar;25(4):529-41
references.pmid: 14735571
references.citation: Science. 1997 Jul 18;277(5324):333-8
references.pmid: 9219684
references.citation: Nature. 1992 Jan 23;355(6358):318-25
references.pmid: 1731246
references.citation: J Mol Biol. 2000 Sep 8;302(1):205-17
references.pmid: 10964570
references.citation: Structure. 2003 Feb;11(2):187-96
references.pmid: 12575938
references.citation: J Biol Chem. 2006 Dec 22;281(51):39380-7
references.pmid: 17050545
references.citation: DNA Repair (Amst). 2008 Jan 1;7(1):1-9
references.pmid: 17716957
references.citation: Biopolymers. 2000-2001;56(4):257-65
references.pmid: 11754339
references.citation: Nucleic Acids Res. 2012 Jun;40(11):4904-13
references.pmid: 22362735
references.citation: Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):9988-93
references.pmid: 15226506
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13248-53
references.pmid: 19587234
references.citation: Nature. 2008 May 22;453(7194):489-4
references.pmid: 18497818
references.citation: Structure. 2012 Mar 7;20(3):440-9
references.pmid: 22405003
references.citation: Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
references.pmid: 9254694
references.citation: J Mol Evol. 1997 May;44(5):528-41
references.pmid: 9115177
references.citation: Nature. 2009 Feb 5;457(7230):745-8
references.pmid: 19060884
references.citation: J Biol Chem. 2001 Oct 19;276(42):38570-81
references.pmid: 11504729
references.citation: Nature. 2002 Nov 21;420(6913):287-93
references.pmid: 12442171
references.citation: J Biol Chem. 2012 Mar 16;287(12):8724-36
references.pmid: 22275364
references.citation: Biochemistry. 2005 Oct 25;44(42):13753-61
references.pmid: 16229465
references.citation: DNA Repair (Amst). 2006 Jun 10;5(6):718-30
references.pmid: 16644292
references.citation: J Comput Chem. 2004 Aug;25(11):1400-15
references.pmid: 15185334
references.citation: Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 2000 Dec;62(6 Pt B):8438-48
references.pmid: 11138145
references.citation: J Mol Biol. 1993 Dec 5;234(3):779-815
references.pmid: 8254673
references.citation: J Biol Chem. 2007 May 11;282(19):14238-42
references.pmid: 17350959
references.citation: Front Biosci. 1998 Jun 17;3:D570-603
references.pmid: 9632377
references.citation: Nucleic Acids Res. 2010 Aug;38(14):4889-906
references.pmid: 20371520
references.citation: Mol Microbiol. 2005 Oct;58(2):358-66
references.pmid: 16194225
references.citation: Nucleic Acids Res. 1997 Dec 15;25(24):4876-82
references.pmid: 9396791
references.citation: Nucleic Acids Res. 2004 Mar 19;32(5):1792-7
references.pmid: 15034147
references.citation: J Am Chem Soc. 2012 May 23;134(20):8447-54
references.pmid: 22548707
references.citation: Nat Struct Mol Biol. 2004 Aug;11(8):791-6
references.pmid: 15235592
references.citation: J Biol Chem. 2005 Jan 7;280(1):722-8
references.pmid: 15537659