Crystal structure of a type III pantothenate kinase: Insight into the mechanism of an essential coenzyme A biosynthetic enzyme universally distributed in bacteria

Simple item page
dc.contributor.authorYang K.
dc.contributor.authorEyobo Y.
dc.contributor.authorBrand L.A.
dc.contributor.authorMartynowski D.
dc.contributor.authorTomchick D.
dc.contributor.authorStrauss E.
dc.contributor.authorZhang H.
dc.date.accessioned2011-05-15T16:01:52Z
dc.date.available2011-05-15T16:01:52Z
dc.date.issued2006
dc.description.abstractPantothenate kinase (PanK) catalyzes the first step in the five-step universal pathway of coenzyme A (CoA) biosynthesis, a key transformation that generally also regulates the intracellular concentration of CoA through feedback inhibition. A novel PanK protein encoded by the gene coaX was recently identified that is distinct from the previously characterized type I PanK (exemplified by the Escherichia coli coaA-encoded PanK protein) and type II eukaryotic PanKs and is not inhibited by CoA or its thioesters. This type III PanK, or PanK-III, is widely distributed in the bacterial kingdom and accounts for the only known PanK in many pathogenic species, such as Helicobacter pylori, Bordetella pertussis, and Pseudomonas aeruginosa. Here we report the first crystal structure of a type III PanK, the enzyme from Thermotoga maritima (PanKTm), solved at 2.0-Å resolution. The structure of PanKTm reveals that type III PanKs belong to the acetate and sugar kinase/heat shock protein 70/actin (ASKHA) protein superfamily and that they retain the highly conserved active site motifs common to all members of this superfamily. Comparative structural analysis of the PanKTm active site configuration and mutagenesis of three highly conserved active site aspartates identify these residues as critical for PanK-III catalysis. Furthermore, the analysis also provides an explanation for the lack of CoA feedback inhibition by the enzyme. Since PanK-III adopts a different structural fold from that of the E. coli PanK-which is a member of the "P-loop kinase" superfamily-this finding represents yet another example of convergent evolution of the same biological function from a different protein ancestor. Copyright © 2006, American Society for Microbiology. All Rights Reserved.
dc.description.versionArticle
dc.identifier.citationJournal of Bacteriology
dc.identifier.citation188
dc.identifier.citation15
dc.identifier.issn219193
dc.identifier.other10.1128/JB.00469-06
dc.identifier.urihttp://hdl.handle.net/10019.1/12194
dc.subjectacetic acid
dc.subjectcoenzyme A
dc.subjectheat shock protein
dc.subjectpantothenate kinase
dc.subjectsugar
dc.subjectthioester
dc.subjectarticle
dc.subjectbacterial gene
dc.subjectBordetella pertussis
dc.subjectcatalysis
dc.subjectcoaX gene
dc.subjectconvergent evolution
dc.subjectcrystal structure
dc.subjectenzyme active site
dc.subjectenzyme activity
dc.subjectenzyme structure
dc.subjectEscherichia coli
dc.subjectHelicobacter pylori
dc.subjectmutagenesis
dc.subjectnegative feedback
dc.subjectnonhuman
dc.subjectnucleotide sequence
dc.subjectpriority journal
dc.subjectprotein family
dc.subjectprotein folding
dc.subjectPseudomonas aeruginosa
dc.subjectstructure analysis
dc.subjectThermotoga maritima
dc.subjectAmino Acid Sequence
dc.subjectBacterial Proteins
dc.subjectBinding Sites
dc.subjectCoenzyme A
dc.subjectModels, Molecular
dc.subjectMolecular Sequence Data
dc.subjectPhosphotransferases (Alcohol Group Acceptor)
dc.subjectSequence Alignment
dc.subjectThermotoga maritima
dc.subjectBacteria (microorganisms)
dc.subjectBordetella pertussis
dc.subjectEscherichia coli
dc.subjectEukaryota
dc.subjectHelicobacter pylori
dc.subjectPseudomonas aeruginosa
dc.subjectThermotoga maritima
dc.titleCrystal structure of a type III pantothenate kinase: Insight into the mechanism of an essential coenzyme A biosynthetic enzyme universally distributed in bacteria
dc.typeArticle
Files
Collections
Stellenbosch University - Scopus Publications