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A path from primary protein sequence to ligand recognition
Author(s) -
Kho Richard,
Baker Brian L.,
Newman Joseph V.,
Jack Richard M.,
Sem Daniel S.,
Villar Hugo O.,
Hansen Mark R.
Publication year - 2003
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.10316
Subject(s) - nad+ kinase , proteome , nicotinamide adenine dinucleotide , enzyme , biology , biochemistry , sequence (biology) , protein family , computational biology , genetics , chemistry , gene
A novel method to organize protein structural information based solely on sequence is presented. The method clusters proteins into families that correlate with the three‐dimensional protein structure and the conformation of the bound ligands. This procedure was applied to nicotinamide adenine dinucleotide [NAD(P)]‐utilizing enzymes to identify a total of 94 sequence families, 53 of which are structurally characterized. Each of the structurally characterized proteins within a sequence family correlates to a single protein fold and to a common bound conformation of NAD(P). A wide range of structural folds is identified that recognize NAD(P), including Rossmann folds and β/α barrels. The defined sequence families can be used to identify the type and prevalence of NAD(P)‐utilizing enzymes in the proteomes of sequenced organisms. The proteome of Mycobacterium tuberculosis was mined to generate a proteome‐wide profile of NAD(P)‐utilizing enzymes coded by this organism. This enzyme family comprises approximately 6% of the open reading frames, with the largest subgroup being the Rossmann fold, short‐chain dehydrogenases. The preponderance of short‐chain dehydrogenases correlates strongly with the phenotype of M. tuberculosis , which is characterized as having one of the most complex prokaryotic cell walls. Proteins 2003;50:589–599. © 2003 Wiley‐Liss, Inc.