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Campylobacter jejuni adenosine triphosphate phosphoribosyltransferase is an active hexamer that is allosterically controlled by the twisting of a regulatory tail
Author(s) -
Mittelstädt Gerd,
Moggré GertJan,
Panjikar Santosh,
Nazmi Ali Reza,
Parker Emily J.
Publication year - 2016
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.2948
Subject(s) - random hexamer , allosteric regulation , adenosine triphosphate , phosphoribosyltransferase , campylobacter jejuni , biochemistry , histidine , chemistry , enzyme , atpase , stereochemistry , biology , mutant , bacteria , hypoxanthine guanine phosphoribosyltransferase , genetics , gene
Adenosine triphosphate phosphoribosyltransferase (ATP‐PRT) catalyzes the first committed step of the histidine biosynthesis in plants and microorganisms. Here, we present the functional and structural characterization of the ATP‐PRT from the pathogenic ε‐proteobacteria Campylobacter jejuni ( Cje ATP‐PRT). This enzyme is a member of the long form (HisG L ) ATP‐PRT and is allosterically inhibited by histidine, which binds to a remote regulatory domain, and competitively inhibited by AMP. In the crystalline form, Cje ATP‐PRT was found to adopt two distinctly different hexameric conformations, with an open homohexameric structure observed in the presence of substrate ATP, and a more compact closed form present when inhibitor histidine is bound. Cje ATP‐PRT was observed to adopt only a hexameric quaternary structure in solution, contradicting previous hypotheses favoring an allosteric mechanism driven by an oligomer equilibrium. Instead, this study supports the conclusion that the ATP‐PRT long form hexamer is the active species; the tightening of this structure in response to remote histidine binding results in an inhibited enzyme.