title: Metal-binding sites are designed to achieve optimal mechanical and signaling properties.
abstract: Many proteins require bound metals to achieve their function. We take advantage of increasing structural data on metal-binding proteins to elucidate three properties: the involvement of metal-binding sites in the global dynamics of the protein, predicted by elastic network models, their exposure/burial to solvent, and their signal-processing properties indicated by Markovian stochastics analysis. Systematic analysis of a data set of 145 structures reveals that the residues that coordinate metal ions enjoy remarkably efficient and precise signal transduction properties. These properties are rationalized in terms of their physical properties: participation in hinge sites that control the softest modes collectively accessible to the protein and occupancy of central positions minimally exposed to solvent. Our observations suggest that metal-binding sites may have been evolutionary selected to achieve optimum allosteric communication. They also provide insights into basic principles for designing metal-binding sites, which are verified to be met by recently designed de novo metal-binding proteins.
authors.affiliation: Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, 3064 BST3, 3501 Fifth Avenue, Pittsburgh, PA 15213, USA.
authors.forename: Anindita
authors.initials: A
authors.lastname: Dutta
authors.forename: Ivet
authors.initials: I
authors.lastname: Bahar
mesh_terms: D001665:Binding Sites; D008390:Markov Chains; D008667:Metalloproteins / Q000737:chemistry* / Q000378:metabolism; D008670:Metals / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D015398:Signal Transduction; D012997:Solvents
chemical_list: D008667:Metalloproteins; D008670:Metals; D012997:Solvents
references.citation: Structure. 2008 Feb;16(2):210-5
references.pmid: 18275812
references.citation: Nucleic Acids Res. 2002 Jan 1;30(1):379-82
references.pmid: 11752342
references.citation: J Am Chem Soc. 2005 Dec 14;127(49):17266-76
references.pmid: 16332076
references.citation: Fold Des. 1997;2(3):173-81
references.pmid: 9218955
references.citation: Protein Sci. 2008 Jan;17(1):54-65
references.pmid: 18042678
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):235-42
references.pmid: 10592235
references.citation: Science. 2008 Jun 13;320(5882):1471-5
references.pmid: 18556554
references.citation: Curr Opin Microbiol. 2001 Apr;4(2):172-7
references.pmid: 11282473
references.citation: Phys Rev Lett. 2006 Feb 24;96(7):078104
references.pmid: 16606146
references.citation: Int J Neural Syst. 2005 Feb-Apr;15(1-2):71-84
references.pmid: 15912584
references.citation: Proteins. 2008 Jan 1;70(1):208-17
references.pmid: 17657805
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14349-54
references.pmid: 19706521
references.citation: Proteins. 2006 Nov 1;65(2):305-16
references.pmid: 16927295
references.citation: Structure. 2005 Jun;13(6):893-904
references.pmid: 15939021
references.citation: Curr Opin Struct Biol. 2007 Dec;17(6):633-40
references.pmid: 18024008
references.citation: BMC Bioinformatics. 2006 Dec 18;7 Suppl 5:S13
references.pmid: 17254297
references.citation: Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1115-22
references.pmid: 11830654
references.citation: Phys Rev Lett. 1996 Aug 26;77(9):1905-1908
references.pmid: 10063201
references.citation: Nature. 2005 Nov 3;438(7064):117-21
references.pmid: 16267559
references.citation: Annu Rev Biophys Biomol Struct. 2006;35:115-33
references.pmid: 16689630
references.citation: J Biol Chem. 2001 Jun 8;276(23):20641-7
references.pmid: 11259434
references.citation: Proteins. 2005 Jan 1;58(1):190-9
references.pmid: 15468317
references.citation: Mol Biosyst. 2008 Apr;4(4):287-92
references.pmid: 18354781
references.citation: BMC Bioinformatics. 2007 Feb 05;8:39
references.pmid: 17280606
references.citation: Bioinformatics. 2002 Oct;18(10):1365-73
references.pmid: 12376381
references.citation: Proteins. 1998 Nov 15;33(3):417-29
references.pmid: 9829700
references.citation: Chem Rev. 2010 Mar 10;110(3):1463-97
references.pmid: 19785456
references.citation: BMC Bioinformatics. 2009 May 08;10:136
references.pmid: 19426475
references.citation: J Comput Chem. 2004 Apr 15;25(5):712-24
references.pmid: 14978714
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):18908-13
references.pmid: 16354836
references.citation: Curr Opin Biotechnol. 1992 Aug;3(4):378-87
references.pmid: 1368439
references.citation: Biophys J. 2002 Aug;83(2):723-32
references.pmid: 12124259
references.citation: Biometals. 2001 Sep-Dec;14(3-4):271-313
references.pmid: 11831461
references.citation: PLoS Comput Biol. 2007 Sep;3(9):1716-26
references.pmid: 17892319