title: Crystal structure of wild-type and mutant human Ap4A hydrolase.
abstract: Ap4A hydrolase (asymmetrical diadenosine tetraphosphate hydrolase, EC 3.6.1.17), an enzyme involved in a number of biological processes, is characterized as cleaving the polyphosphate chain at the fourth phosphate from the bound adenosine moiety. This paper presents the crystal structure of wild-type and E58A mutant human Ap4A hydrolase. Similar to the canonical Nudix fold, human Ap4A hydrolase shows the common αβα-sandwich architecture. Interestingly, two sulfate ions and one diphosphate coordinated with some conserved residues were observed in the active cleft, which affords a better understanding of a possible mode of substrate binding.
authors: Institute of Health Sciences and Modern Experiment Technology Center, Anhui University, Hefei 230601, People's Republic of China. hhge@ahu.edu.cn
authors: Honghua
authors: H
authors: Ge
authors: Xiaofang
authors: X
authors: Chen
authors: Weili
authors: W
authors: Yang
authors: Liwen
authors: L
authors: Niu
authors: Maikun
authors: M
authors: Teng
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000737:chemistry* / Q000235:genetics*; D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D011756:Diphosphates / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry; D009154:Mutation; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry* / Q000235:genetics*; D017433:Protein Structure, Secondary; D013463:Sulfuric Acid Esters / Q000737:chemistry; D000096964:Nudix Hydrolases
chemical_list: D017766:Acid Anhydride Hydrolases; D011756:Diphosphates; D050505:Mutant Proteins; D010744:Phosphoric Monoester Hydrolases; D013463:Sulfuric Acid Esters; C557514:NUDT2 protein, human; D000096964:Nudix Hydrolases; C020023:bis(5'-nucleosyl)tetraphosphatase (asymmetrical)
references: Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):235-42
references: 21460441
references: Acta Crystallogr D Biol Crystallogr. 1997 May 1;53(Pt 3):240-55
references: 15299926
references: Proteins. 2003 Feb 15;50(3):437-50
references: 12557186
references: Methods Enzymol. 1997;276:307-26
references: 27754618
references: Bioinformatics. 1999 Apr;15(4):305-8
references: 10320398
references: J Biol Chem. 2004 Jun 4;279(23):24861-5
references: 15060060
references: Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):271-81
references: 21460445
references: FEBS Lett. 1998 May 8;427(2):157-63
references: 9607303
references: Int J Mol Med. 1999 Jul;4(1):79-89
references: 10373642
references: FEBS Lett. 1997 Sep 29;415(2):160-2
references: 9350987
references: Nucleic Acids Res. 1988 Nov 25;16(22):10881-90
references: 2849754
references: Cell. 1983 Oct;34(3):711-2
references: 6354469
references: Bioinformatics. 2003 Jan 22;19(2):311-2
references: 12538265
references: Mol Microbiol. 2000 Apr;36(1):174-82
references: 10760174
references: Pharmacol Ther. 2000 Aug-Sep;87(2-3):73-89
references: 11007992
references: Structure. 2002 Apr;10(4):589-600
references: 11937063
references: Proc Natl Acad Sci U S A. 1976 Nov;73(11):3984-8
references: 1069282
references: Curr Med Chem Cardiovasc Hematol Agents. 2003 Jun;1(2):151-69
references: 15320695
references: Trends Biochem Sci. 1998 May;23(5):157-9
references: 9612076
references: Pharmacol Ther. 2000 Aug-Sep;87(2-3):103-15
references: 11007994
references: J Biol Chem. 2003 Aug 29;278(35):32602-7
references: 12824172
references: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
references: 15572765
references: Biochim Biophys Acta. 2001 Nov 26;1550(1):27-36
references: 11738085
references: J Biol Chem. 2005 Mar 4;280(9):8471-81
references: 15596429
references: Virol J. 2010 Feb 09;7:31
references: 20144233
references: J Pharmacol Toxicol Methods. 1995 Jun;33(3):121-8
references: 7640391
references: Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):116-24
references: 20124691
references: Proc Natl Acad Sci U S A. 1983 Dec;80(24):7496-500
references: 6369319
references: J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
references: 19461840
references: J Mol Biol. 1968 Apr 28;33(2):491-7
references: 5700707
references: Mol Cell Biol. 2008 Sep;28(18):5777-84
references: 18644867
references: Structure. 2002 Feb;10(2):205-13
references: 11839306