title: On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm.
abstract: N-acetyl-L-glutamate kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequence-->structure-->dynamics-->function.
authors.affiliation: Department of Biological Chemistry and Molecular Modelling, IQAC-CSIC, Barcelona, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Marcos
authors.forename: Ramon
authors.initials: R
authors.lastname: Crehuet
authors.forename: Ivet
authors.initials: I
authors.lastname: Bahar
mesh_terms: D000494:Allosteric Regulation; D016880:Anisotropy; D020134:Catalytic Domain; D019295:Computational Biology / Q000379:methods*; D008390:Markov Chains; D056004:Molecular Dynamics Simulation; D016011:Normal Distribution; D017851:Phosphotransferases (Carboxyl Group Acceptor) / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship
chemical_list: D017851:Phosphotransferases (Carboxyl Group Acceptor); C018721:acetylglutamate kinase
references.citation: Proteins. 2009 Dec;77(4):927-39
references.pmid: 19688820
references.citation: Protein Sci. 2008 May;17(5):918-29
references.pmid: 18369194
references.citation: Bioinformatics. 2008 Dec 1;24(23):2780-1
references.pmid: 18818215
references.citation: Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W610-4
references.pmid: 15215461
references.citation: Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2794-9
references.pmid: 11867722
references.citation: Nat Chem Biol. 2008 Aug;4(8):474-82
references.pmid: 18641628
references.citation: Structure. 2007 Feb;15(2):169-77
references.pmid: 17292835
references.citation: Science. 2005 Jun 3;308(5727):1424-8
references.pmid: 15933191
references.citation: Biophys J. 2002 Nov;83(5):2457-74
references.pmid: 12414680
references.citation: PLoS Comput Biol. 2007 Sep;3(9):1716-26
references.pmid: 17892319
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11182-7
references.pmid: 18678900
references.citation: Protein Eng. 2001 Jan;14(1):1-6
references.pmid: 11287673
references.citation: J Mol Biol. 2003 Nov 28;334(3):459-76
references.pmid: 14623187
references.citation: J Mol Biol. 2003 Oct 10;333(1):153-68
references.pmid: 14516750
references.citation: Biophys J. 2001 Jan;80(1):505-15
references.pmid: 11159421
references.citation: J Mol Biol. 2003 Aug 1;331(1):231-44
references.pmid: 12875848
references.citation: J Mol Biol. 1996 Aug 23;261(3):490-506
references.pmid: 8780788
references.citation: Structure. 2007 May;15(5):565-75
references.pmid: 17502102
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14349-54
references.pmid: 19706521
references.citation: J Mol Graph. 1996 Feb;14(1):33-8, 27-8
references.pmid: 8744570
references.citation: Bioinformatics. 2009 Aug 1;25(15):1876-83
references.pmid: 19487258
references.citation: Structure. 2005 Jun;13(6):893-904
references.pmid: 15939021
references.citation: J Mol Biol. 2000 Jun 2;299(2):463-76
references.pmid: 10860751
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12730-5
references.pmid: 16129832
references.citation: Nature. 2007 Dec 13;450(7172):964-72
references.pmid: 18075575
references.citation: J Mol Biol. 2005 Sep 16;352(2):438-54
references.pmid: 16095620
references.citation: Biochemistry. 2007 Dec 25;46(51):15076-88
references.pmid: 18052079
references.citation: Fold Des. 1997;2(3):173-81
references.pmid: 9218955
references.citation: Biophys J. 2005 Jul;89(1):167-78
references.pmid: 15879477
references.citation: Structure. 2008 Feb;16(2):321-30
references.pmid: 18275822
references.citation: Biophys J. 2009 Jan;96(2):464-75
references.pmid: 19167297
references.citation: Proteins. 2002 Sep 1;48(4):682-95
references.pmid: 12211036
references.citation: Mol Syst Biol. 2006;2:36
references.pmid: 16820777
references.citation: Eur J Biochem. 1975 Mar 17;52(2):377-93
references.pmid: 240684
references.citation: Proc Natl Acad Sci U S A. 1958 Feb;44(2):98-104
references.pmid: 16590179
references.citation: Annu Rev Biophys Biomol Struct. 2006;35:115-33
references.pmid: 16689630
references.citation: Bioinformatics. 2006 Nov 1;22(21):2619-27
references.pmid: 16928735
references.citation: Bioinformatics. 2009 Mar 1;25(5):606-14
references.pmid: 19147661
references.citation: J Mol Biol. 2006 Feb 24;356(3):695-713
references.pmid: 16376937
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):13829-34
references.pmid: 18772387
references.citation: Structure. 2002 Mar;10(3):329-42
references.pmid: 12005432
references.citation: J Mol Biol. 1996 May 3;258(2):393-410
references.pmid: 8627633
references.citation: Nat Struct Biol. 2003 Jan;10(1):59-69
references.pmid: 12483203
references.citation: Science. 2008 Jun 13;320(5882):1471-5
references.pmid: 18556554
references.citation: Curr Opin Struct Biol. 2005 Oct;15(5):586-92
references.pmid: 16143512
references.citation: Proc Natl Acad Sci U S A. 2006 May 16;103(20):7664-9
references.pmid: 16682636
references.citation: Microb Cell Fact. 2006 Jan 12;5:2
references.pmid: 16409630
references.citation: Chem Rev. 2006 Aug;106(8):3210-35
references.pmid: 16895325
references.citation: Phys Rev Lett. 2006 Feb 24;96(7):078104
references.pmid: 16606146
references.citation: Science. 2002 Feb 22;295(5559):1520-3
references.pmid: 11859194
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):18908-13
references.pmid: 16354836
references.citation: Biophys J. 2002 Aug;83(2):723-32
references.pmid: 12124259
references.citation: J Bacteriol. 2008 Apr;190(8):3018-25
references.pmid: 18263723
references.citation: J Mol Biol. 2006 Apr 21;358(1):213-23
references.pmid: 16513135
references.citation: Nat Struct Mol Biol. 2004 Oct;11(10):945-9
references.pmid: 15334070
references.citation: J Mol Biol. 1965 May;12:88-118
references.pmid: 14343300
references.citation: FEBS Lett. 2007 Jun 19;581(15):2776-82
references.pmid: 17531981