title: Ultrafast water dynamics at the interface of the polymerase-DNA binding complex.
abstract: DNA polymerases slide on DNA during replication, and the interface must be mobile for various conformational changes. The role of lubricant interfacial water is not understood. In this report, we systematically characterize the water dynamics at the interface and in the active site of a tight binding polymerase (pol β) in its binary complex and ternary state using tryptophan as a local optical probe. Using femtosecond spectroscopy, we observed that upon DNA recognition the surface hydration water is significantly confined and becomes bound water at the interface, but the dynamics are still ultrafast and occur on the picosecond time scale. These interfacial water molecules are not trapped but are mobile in the heterogeneous binding nanospace. Combining our findings with our previous observation of ultrafast water motions at the interface of a loose binding polymerase (Dpo4), we conclude that the binding interface is dynamic and the water molecules in various binding clefts, channels, and caves are mobile and even fluid with different levels of mobility for loose or tight binding polymerases. Such a dynamic interface should be general to all DNA polymerase complexes to ensure the biological function of DNA synthesis.
authors.affiliation: Department of Physics, ‡Department of Chemistry and Biochemistry, and §Programs of Biophysics, Chemical Physics, and Biochemistry, The Ohio State University , Columbus, Ohio 43210, United States.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Yangzhong
authors.initials: Y
authors.lastname: Qin
authors.forename: Qing
authors.initials: Q
authors.lastname: Ding
authors.forename: Marina
authors.initials: M
authors.lastname: Bakhtina
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.forename: Ming-Daw
authors.initials: MD
authors.lastname: Tsai
authors.forename: Dongping
authors.initials: D
authors.lastname: Zhong
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D019951:DNA Polymerase beta / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D009154:Mutation; D051381:Rats; D013050:Spectrometry, Fluorescence; D014867:Water / Q000737:chemistry*
chemical_list: D029968:Escherichia coli Proteins; D014867:Water; C509838:Dpo4 protein, E coli; D019951:DNA Polymerase beta
references.citation: J Am Chem Soc. 2012 Oct 10;134(40):16460-3
references.pmid: 22992183
references.citation: J Phys Chem B. 2006 Jun 1;110(21):10540-9
references.pmid: 16722765
references.citation: Chem Rev. 2006 Feb;106(2):361-82
references.pmid: 16464010
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18461-6
references.pmid: 18003912
references.citation: Cell. 1992 May 1;69(3):425-37
references.pmid: 1349852
references.citation: Cell. 2001 Jun 1;105(5):657-67
references.pmid: 11389835
references.citation: Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):10964-9
references.pmid: 12177425
references.citation: J Mol Biol. 2012 Jun 8;419(3-4):171-82
references.pmid: 22446382
references.citation: Science. 1994 Jun 24;264(5167):1891-903
references.pmid: 7516580
references.citation: Biochemistry. 2014 May 6;53(17):2768-80
references.pmid: 24717170
references.citation: Biochemistry. 1997 Sep 30;36(39):11891-900
references.pmid: 9305982
references.citation: J Phys Chem B. 2009 Jun 18;113(24):8210-3
references.pmid: 19462949
references.citation: J Am Chem Soc. 2008 Oct 1;130(39):13103-9
references.pmid: 18767841
references.citation: Biochem J. 1997 Apr 1;323 ( Pt 1):103-11
references.pmid: 9173867
references.citation: J Am Chem Soc. 2007 Mar 21;129(11):3376-82
references.pmid: 17319669
references.citation: J Am Chem Soc. 2003 Jul 9;125(27):8163-77
references.pmid: 12837086
references.citation: Nat Struct Mol Biol. 2009 Dec;16(12):1224-9
references.pmid: 19898474
references.citation: Annu Rev Biochem. 1995;64:171-200
references.pmid: 7574479
references.citation: Chemphyschem. 2001 Apr 17;2(4):219-27
references.pmid: 23696483
references.citation: Biophys J. 2004 Jun;86(6):3392-408
references.pmid: 15189842
references.citation: J Am Chem Soc. 2004 Jul 14;126(27):8441-53
references.pmid: 15238001
references.citation: J Phys Chem B. 2012 Nov 15;116(45):13320-30
references.pmid: 23075091
references.citation: Biochem J. 1998 Apr 1;331 ( Pt 1):79-87
references.pmid: 9512464
references.citation: Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):13979-84
references.pmid: 16968773
references.citation: Biochemistry. 2014 May 6;53(17):2749-51
references.pmid: 24716436
references.citation: J Mol Biol. 2000 Feb 11;296(1):229-53
references.pmid: 10656829
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5970-5
references.pmid: 15069184
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15297-302
references.pmid: 12427971
references.citation: J Mol Biol. 2001 Nov 30;314(3):619-32
references.pmid: 11846571
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):715-20
references.pmid: 20080740
references.citation: Curr Opin Struct Biol. 1997 Feb;7(1):126-34
references.pmid: 9032063
references.citation: J Am Chem Soc. 2007 Apr 18;129(15):4731-7
references.pmid: 17375926
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13867-72
references.pmid: 16162674
references.citation: J Phys Chem A. 2013 Dec 19;117(50):13926-34
references.pmid: 24308461
references.citation: J Phys Chem B. 2008 Dec 18;112(50):16121-34
references.pmid: 19368022
references.citation: Biochim Biophys Acta. 2010 May;1804(5):1136-50
references.pmid: 19631767
references.citation: Science. 1994 Jun 24;264(5167):1930-5
references.pmid: 7516581
references.citation: Cell. 1996 Jun 28;85(7):1057-65
references.pmid: 8674112
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5366-71
references.pmid: 17369362
references.citation: Biochemistry. 1988 Feb 9;27(3):901-9
references.pmid: 3284575
references.citation: Science. 2011 Dec 23;334(6063):1675-80
references.pmid: 22194570
references.citation: Annu Rev Biophys Biomol Struct. 2006;35:389-415
references.pmid: 16689642
references.citation: Science. 1994 Dec 23;266(5193):2022-5
references.pmid: 7528445
references.citation: J Am Chem Soc. 2009 Aug 5;131(30):10677-91
references.pmid: 19586028
references.citation: Biochemistry. 1996 Oct 1;35(39):12742-61
references.pmid: 8841118
references.citation: J Mol Biol. 2002 Jun 21;319(5):1097-113
references.pmid: 12079350
references.citation: Biochemistry. 1996 Jun 4;35(22):7041-50
references.pmid: 8679529
references.citation: Annu Rev Phys Chem. 2009;60:217-39
references.pmid: 19012538
references.citation: Structure. 1999 Dec 15;7(12):R277-9
references.pmid: 10647173
references.citation: Biochemistry. 1997 Sep 16;36(37):11205-15
references.pmid: 9287163
references.citation: J Am Chem Soc. 2009 Jan 21;131(2):494-501
references.pmid: 19113888
references.citation: Cell. 2013 Jul 3;154(1):157-68
references.pmid: 23827680
references.citation: J Phys Chem B. 2005 Sep 8;109(35):16901-10
references.pmid: 16853151
references.citation: J Mol Biol. 1998 Oct 2;282(4):847-58
references.pmid: 9743631
references.citation: Annu Rev Biophys Biomol Struct. 2004;33:343-61
references.pmid: 15139817
references.citation: Biophys J. 1997 Aug;73(2):557-70
references.pmid: 9251777
references.citation: Structure. 2012 Nov 7;20(11):1829-37
references.pmid: 22959623
references.citation: Science. 1991 Nov 15;254(5034):974-80
references.pmid: 1948083
references.citation: Nat Struct Mol Biol. 2011 Feb;18(2):245-9
references.pmid: 21196937
references.citation: Biochemistry. 2006 Dec 26;45(51):15142-56
references.pmid: 17176036
references.citation: J Am Chem Soc. 2005 May 4;127(17):6257-65
references.pmid: 15853331
references.citation: J Phys Chem B. 2006 Sep 21;110(37):18097-103
references.pmid: 16970418
references.citation: J Am Chem Soc. 2008 Oct 8;130(40):13240-50
references.pmid: 18785738