Protein sequence alignments: a strategy for the hierarchical analysis of residue conservation
Laboratory of Molecular Biophysics, University of Oxford Rex Richards Building, South Parks Road, Oxford OX] 3QU, UK
1To whom correspondence should be addressed
An algorithm is described for the systematic characterization of the physico-chemical properties seen at each position in a multiple protein sequence alignment. The new algorithm allows questions important in the design of muta genesis experiments to be quickly answered since positions in the align that show unusual or interesting residue substitution patterns may be rapidly identified. The strategy is based on a flexible set-based description of amino acid properties, which is used to define the conservation between any group of amino acids. Sequences in the alignment are gathered into subgroups on the basis of sequence similariiy, functional, evolutionary or other criteria. All pairs of subgroups are then compared to highlight positions that confer the unique features of each subgroup. The algorithm is encoded in the computer program AMAS (Analysis of Multiply Aligned Sequences) which provides a textual summary of the analysis and an annotated (boxed, shaded and/or coloured) multiple sequence alignment. The algorithm is illustrated by application to an alignment of 67 SH2 domains where patterns of conserved hydrophobic residues that constitute the protein core are highlighted. The analysis of charge conservation across annexin domains identifies the locations at which conserved charges change sign. The algorithm simplifies the analysis of multiple sequence data by condensing the mass of information present, and thus allows the rapid identification of substitutions of structural and functional importance.
Received on May 23, 1993; accepted on August 5, 1993
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  P. K. Baral, N. Jajcanin-Jozic, S. Deller, P. Macheroux, M. Abramic, and K. Gruber The First Structure of Dipeptidyl-peptidase III Provides Insight into the Catalytic Mechanism and Mode of Substrate Binding J. Biol. Chem., August 8, 2008; 283(32): 22316 - 22324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Capra and M. Singh Characterization and prediction of residues determining protein functional specificity Bioinformatics, July 1, 2008; 24(13): 1473 - 1480. [Abstract] [PDF]
|
|
|
|
 |
|
 D. C. Fulton, M. Stettler, T. Mettler, C. K. Vaughan, J. Li, P. Francisco, M. Gil, H. Reinhold, S. Eicke, G. Messerli, et al. {beta}-AMYLASE4, a Noncatalytic Protein Required for Starch Breakdown, Acts Upstream of Three Active {beta}-Amylases in Arabidopsis Chloroplasts PLANT CELL, April 1, 2008; 20(4): 1040 - 1058. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Ai, A. Semesi, A. Yee, C. H. Arrowsmith, W.-Y. Choy, and S. S.C. Li The hypothetical protein Atu4866 from Agrobacterium tumefaciens adopts a streptavidin-like fold Protein Sci., January 1, 2008; 17(1): 154 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Anderson, P. Adhikari, K. D. Weaver, A. L. Crumbliss, and T. A. Mietzner The Haemophilus influenzae hFbpABC Fe3+ Transporter: Analysis of the Membrane Permease and Development of a Gallium-Based Screen for Mutants J. Bacteriol., July 15, 2007; 189(14): 5130 - 5141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Mirabeau, E. Perlas, C. Severini, E. Audero, O. Gascuel, R. Possenti, E. Birney, N. Rosenthal, and C. Gross Identification of novel peptide hormones in the human proteome by hidden Markov model screening Genome Res., March 1, 2007; 17(3): 320 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Phuong, C. B. Do, R. C. Edgar, and S. Batzoglou Multiple alignment of protein sequences with repeats and rearrangements Nucleic Acids Res., November 6, 2006; 34(20): 5932 - 5942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Mercante, K. Suzuki, X. Cheng, P. Babitzke, and T. Romeo Comprehensive Alanine-scanning Mutagenesis of Escherichia coli CsrA Defines Two Subdomains of Critical Functional Importance J. Biol. Chem., October 20, 2006; 281(42): 31832 - 31842. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Monnier, K. Higo-Moriguchi, Z.-Y. J. Sun, B. V. V. Prasad, K. Taniguchi, and P. R. Dormitzer High-Resolution Molecular and Antigen Structure of the VP8* Core of a Sialic Acid-Independent Human Rotavirus Strain J. Virol., February 1, 2006; 80(3): 1513 - 1523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Pei, W. Cai, L. N. Kinch, and N. V. Grishin Prediction of functional specificity determinants from protein sequences using log-likelihood ratios Bioinformatics, January 15, 2006; 22(2): 164 - 171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Edwards and D. C. Shields BADASP: predicting functional specificity in protein families using ancestral sequences Bioinformatics, November 15, 2005; 21(22): 4190 - 4191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Moreno, E. Hebrard, M. Uzest, S. Blanc, and A. Fereres A Single Amino Acid Position in the Helper Component of Cauliflower Mosaic Virus Can Change the Spectrum of Transmitting Vector Species J. Virol., November 1, 2005; 79(21): 13587 - 13593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Hoppner, A. Carle, D. Sivanesan, S. Hoeppner, and C. Baron The putative lytic transglycosylase VirB1 from Brucella suis interacts with the type IV secretion system core components VirB8, VirB9 and VirB11 Microbiology, November 1, 2005; 151(11): 3469 - 3482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. George, R. V. Spriggs, G. J. Bartlett, A. Gutteridge, M. W. MacArthur, C. T. Porter, B. Al-Lazikani, J. M. Thornton, and M. B. Swindells Inaugural Article: Effective function annotation through catalytic residue conservation PNAS, August 30, 2005; 102(35): 12299 - 12304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. A. Ivanisenko, A. M. Eroshkin, and N. A. Kolchanov WebProAnalyst: an interactive tool for analysis of quantitative structure-activity relationships in protein families Nucleic Acids Res., July 1, 2005; 33(suppl_2): W99 - W104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Bradford and D. R. Westhead Improved prediction of protein-protein binding sites using a support vector machines approach Bioinformatics, April 15, 2005; 21(8): 1487 - 1494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kannan and A. F. Neuwald Evolutionary constraints associated with functional specificity of the CMGC protein kinases MAPK, CDK, GSK, SRPK, DYRK, and CK2{alpha} Protein Sci., August 1, 2004; 13(8): 2059 - 2077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. V. Kalinina, P. S. Novichkov, A. A. Mironov, M. S. Gelfand, and A. B. Rakhmaninova SDPpred: a tool for prediction of amino acid residues that determine differences in functional specificity of homologous proteins Nucleic Acids Res., July 1, 2004; 32(suppl_2): W424 - W428. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ichihara, H. Daiyasu, and H. Toh How does a topological inversion change the evolutionary constraints on membrane proteins? Protein Eng. Des. Sel., March 1, 2004; 17(3): 235 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Thompson, V. Prigent, and O. Poch LEON: multiple aLignment Evaluation Of Neighbours Nucleic Acids Res., February 24, 2004; 32(4): 1298 - 1307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. I. Zaika, R. A. Perlow, E. Matz, S. Broyde, R. Gilboa, A. P. Grollman, and D. O. Zharkov Substrate Discrimination by Formamidopyrimidine-DNA Glycosylase: A MUTATIONAL ANALYSIS J. Biol. Chem., February 6, 2004; 279(6): 4849 - 4861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. V. Kalinina, A. A. Mironov, M. S. Gelfand, and A. B. Rakhmaninova Automated selection of positions determining functional specificity of proteins by comparative analysis of orthologous groups in protein families Protein Sci., February 1, 2004; 13(2): 443 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dong, Z. Li, M. Zang, D. I. Pinon, T. P. Lybrand, and L. J. Miller Spatial Approximation between Two Residues in the Mid-region of Secretin and the Amino Terminus of Its Receptor: INCORPORATION OF SEVEN SETS OF SUCH CONSTRAINTS INTO A THREE-DIMENSIONAL MODEL OF THE AGONIST-BOUND SECRETIN RECEPTOR J. Biol. Chem., November 28, 2003; 278(48): 48300 - 48312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Nanao, W. Zhou, P. J. Pfaffinger, and S. Choe Determining the basis of channel-tetramerization specificity by x-ray crystallography and a sequence-comparison algorithm: Family values (FamVal) PNAS, July 22, 2003; 100(15): 8670 - 8675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gilboa, D. O. Zharkov, G. Golan, A. S. Fernandes, S. E. Gerchman, E. Matz, J. H. Kycia, A. P. Grollman, and G. Shoham Structure of Formamidopyrimidine-DNA Glycosylase Covalently Complexed to DNA J. Biol. Chem., May 24, 2002; 277(22): 19811 - 19816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Godsey, N. N. Baranova, A. A. Neyfakh, and R. G. Brennan Crystal Structure of MtaN, a Global Multidrug Transporter Gene Activator J. Biol. Chem., December 7, 2001; 276(50): 47178 - 47184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Manoj and K. Suguna Signature of quaternary structure in the sequences of legume lectins Protein Eng. Des. Sel., October 1, 2001; 14(10): 735 - 745. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Karmirantzou and S.J. Hamodrakas A Web-based classification system of DNA-binding protein families Protein Eng. Des. Sel., July 1, 2001; 14(7): 465 - 472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Peelman, B. Vanloo, J.-L. Verschelde, C. Labeur, H. Caster, J. Taveirne, A. Verhee, N. Duverger, J. Vandekerckhove, J. Tavernier, et al. Effect of mutations of N- and C-terminal charged residues on the activity of LCAT J. Lipid Res., April 1, 2001; 42(4): 471 - 479. [Abstract] [Full Text]
|
|
|
|
|
|
P. Lucas, C. Otis, J.-P. Mercier, M. Turmel, and C. Lemieux Rapid evolution of the DNA-binding site in LAGLIDADG homing endonucleases Nucleic Acids Res., February 15, 2001; 29(4): 960 - 969. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Hyman, H. Chen, P. P. Di Fiore, P. De Camilli, and A. T. Brunger Epsin 1 Undergoes Nucleocytosolic Shuttling and its Eps15 Interactor NH2-terminal Homology (ENTH) Domain, Structurally Similar to Armadillo and HEAT Repeats, Interacts with the Transcription Factor Promyelocytic Leukemia Zn2+ Finger Protein (PLZF) J. Cell Biol., May 1, 2000; 149(3): 537 - 546. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C.W. May Towards more meaningful hierarchical classification of amino acid scoring matrices Protein Eng. Des. Sel., September 1, 1999; 12(9): 707 - 712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. N. Krath and B. Hove-Jensen Organellar and Cytosolic Localization of Four Phosphoribosyl Diphosphate Synthase Isozymes in Spinach Plant Physiology, February 1, 1999; 119(2): 497 - 506. [Abstract] [Full Text]
|
|
|
|
|
|
F. Peelman, J-L. Verschelde, B. Vanloo, C. Ampe, C. Labeur, J. Tavernier, J. Vandekerckhove, and M. Rosseneu Effects of natural mutations in lecithin:cholesterol acyltransferase on the enzyme structure and activity J. Lipid Res., January 1, 1999; 40(1): 59 - 69. [Abstract] [Full Text]
|
|
|
|
 |
|
 B. Nagar, R. G. Jones, R. J. Diefenbach, D. E. Isenman, and J. M. Rini X-ray Crystal Structure of C3d: A C3 Fragment and Ligand for Complement Receptor 2 Science, May 22, 1998; 280(5367): 1277 - 1281. [Abstract] [Full Text]
|
|
|
|
|
|
B. Staskawicz, F. Ausubel, B. Baker, J. Ellis, and J. Jones Molecular genetics of plant disease resistance Science, May 5, 1995; 268(5211): 661 - 667. [Abstract] [PDF]
|
|
|
|
|
|
Y. Paz, Z. Elazar, and D. Fass Structure of GATE-16, Membrane Transport Modulator and Mammalian Ortholog of Autophagocytosis Factor Aut7p J. Biol. Chem., August 11, 2000; 275(33): 25445 - 25450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Desrumaux, C. Labeur, A. Verhee, J. Tavernier, J. Vandekerckhove, M. Rosseneu, and F. Peelman A Hydrophobic Cluster at the Surface of the Human Plasma Phospholipid Transfer Protein Is Critical for Activity on High Density Lipoproteins J. Biol. Chem., February 16, 2001; 276(8): 5908 - 5915. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Johnson and G. M. Church Predicting ligand-binding function in families of bacterial receptors PNAS, April 11, 2000; 97(8): 3965 - 3970. [Abstract] [Full Text] [PDF]
|
|