title: Conserved water-mediated H-bonding dynamics of catalytic His159 and Asp158: insight into a possible acid-base coupled mechanism in plant thiol protease.
abstract: Cysteine protease is ubiquitous in nature. Excess activity of this enzyme causes intercellular proteolysis, muscle tissue degradation, etc. The role of water-mediated interactions in the stabilization of catalytically significant Asp158 and His159 was investigated by performing molecular dynamics simulation studies of 16 three-dimensional structures of plant thiol proteases. In the simulated structures, the hydrophilic W(1), W(2) and WD(1) centers form hydrogen bonds with the OD1 atom of Asp158 and the ND1 atom of His159. In the solvated structures, another water molecule, W(E), forms a hydrogen bond with the NE2 atom of His159. In the absence of the water molecule W(E), Trp177 (NE1) and Gln19 (NE2) directly interact with the NE2 atom of His159. All these hydrophilic centers (the locations of W(1), W(2), WD(1), and W(E)) are conserved, and they play a critical role in the stabilization of His-Asp complexes. In the water dynamics of solvated structures, the water molecules W(1) and W(2) form a water...water hydrogen-bonded network with a few other water molecules. A few dynamical conformations or transition states involving direct (His159 ND1...Asp158 OD1) and water-mediated (His159 ND1...W(2)...Asp158 OD1) hydrogen-bonded complexes are envisaged from these studies.
authors.affiliation: Department of Chemistry, National Institute of Technology, Durgapur, India.
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Nandi
authors.forename: Hridoy R
authors.initials: HR
authors.lastname: Bairagya
authors.forename: Bishnu P
authors.initials: BP
authors.lastname: Mukhopadhyay
authors.forename: Payel
authors.initials: P
authors.lastname: Mallik
authors.forename: Dipankar
authors.initials: D
authors.lastname: Sukul
authors.forename: Asim K
authors.initials: AK
authors.lastname: Bera
mesh_terms: D020816:Amino Acid Motifs; D001224:Aspartic Acid / Q000737:chemistry*; D055162:Biocatalysis; D020134:Catalytic Domain; D057056:Cysteine Proteases / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D010940:Plant Proteins / Q000737:chemistry*; D011485:Protein Binding; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
chemical_list: D010940:Plant Proteins; D014867:Water; D001224:Aspartic Acid; D006639:Histidine; D057056:Cysteine Proteases
references.citation: Chem Rev. 2002 Dec;102(12):4459-88
references.pmid: 12475197
references.citation: J Mol Graph. 1996 Feb;14(1):33-8, 27-8
references.pmid: 8744570
references.citation: Biochemistry. 1995 Oct 10;34(40):13190-5
references.pmid: 7548082
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):235-42
references.pmid: 10592235
references.citation: Biochemistry. 1991 Jun 4;30(22):5531-8
references.pmid: 2036422
references.citation: FEBS Lett. 1974 Oct 1;47(1):15-8
references.pmid: 4426388
references.citation: Proteins. 2003 Jun 1;51(4):489-97
references.pmid: 12784208
references.citation: J Am Chem Soc. 2008 Jul 9;130(27):8696-705
references.pmid: 18557615
references.citation: Protein Eng Des Sel. 2004 Mar;17(3):223-34
references.pmid: 15115851
references.citation: Clin Chem. 1992 Sep;38(9):1694-7
references.pmid: 1526000
references.citation: J Pept Res. 2004 Oct;64(4):141-50
references.pmid: 15357669
references.citation: Exp Neurol. 1986 Sep;93(3):642-6
references.pmid: 3743709
references.citation: J Med Chem. 1998 Nov 5;41(23):4567-76
references.pmid: 9804696
references.citation: Protein Sci. 2005 Jan;14(1):111-8
references.pmid: 15576559
references.citation: Biochemistry. 1992 Jun 9;31(22):5172-6
references.pmid: 1606141
references.citation: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W382-8
references.pmid: 15980494
references.citation: J Biol Chem. 1995 Jul 14;270(28):16645-52
references.pmid: 7622473
references.citation: J Comput Chem. 2005 Dec;26(16):1781-802
references.pmid: 16222654
references.citation: Biochem J. 2007 Jan 15;401(2):421-8
references.pmid: 17007609
references.citation: J Biomol Struct Dyn. 2009 Feb;26(4):497-507
references.pmid: 19108589
references.citation: Cancer Metastasis Rev. 1990 Dec;9(4):333-52
references.pmid: 2097084
references.citation: Biochem J. 1992 Nov 1;287 ( Pt 3):797-803
references.pmid: 1445241
references.citation: J Biol Chem. 1991 Aug 5;266(22):14771-7
references.pmid: 1860874
references.citation: Biochemistry. 1999 Sep 7;38(36):11624-33
references.pmid: 10512617
references.citation: Proteins. 2004 Oct 1;57(1):1-8
references.pmid: 15326588
references.citation: J Mol Biol. 1984 Oct 25;179(2):233-56
references.pmid: 6502713
references.citation: FEBS Lett. 1996 Aug 19;392(1):35-9
references.pmid: 8769310
references.citation: Biophys J. 2003 Apr;84(4):2207-15
references.pmid: 12668429
references.citation: J Biosci. 2009 Mar;34(1):27-34
references.pmid: 19430116
references.citation: Biochem Biophys Res Commun. 2007 Nov 3;362(4):965-70
references.pmid: 17767923
references.citation: Biochemistry. 2008 Feb 19;47(7):2025-35
references.pmid: 18225918
references.citation: Protein Sci. 2003 Apr;12(4):794-810
references.pmid: 12649438
references.citation: Chem Rev. 1997 Feb 5;97(1):133-172
references.pmid: 11848867
references.citation: J Biomol Struct Dyn. 2009 Oct;27(2):149-58
references.pmid: 19583440
references.citation: Biochemistry. 1996 Dec 17;35(50):16292-8
references.pmid: 8973203