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PubMed · 12577265

A path from primary protein sequence to ligand recognition.

Richard Kho·Brian L Baker·Joseph V Newman·Richard M Jack·Daniel S Sem·Hugo O Villar·Mark R Hansen
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Abstract

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 beta/alpha 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.

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Amino Acid SequenceBacterial ProteinsBinding SitesCluster AnalysisEnzymesFlavinsGene FrequencyGenome, BacterialLigandsModels, MolecularMycobacterium tuberculosisNADPNADPH DehydrogenaseOxidoreductasesProtein ConformationProtein FoldingProteinsProteomeSequence Analysis, ProteinJournal Article

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Richard Kho, Brian L Baker, Joseph V Newman, Richard M Jack, Daniel S Sem, Hugo O Villar, Mark R Hansen. 2003-03-01. A path from primary protein sequence to ligand recognition.. https://doi.org/10.1002/prot.10316

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