Swiveling-domain mechanism for enzymatic phosphotransfer between remote reaction sites.

Printer-friendly versionPrinter-friendly versionPDF versionPDF version
TitleSwiveling-domain mechanism for enzymatic phosphotransfer between remote reaction sites.
Publication TypeJournal Article
Year of Publication1996
AuthorsHerzberg, O, Chen, CC, Kapadia, G, McGuire, M, Carroll, LJ, Noh, SJ, Dunaway-Mariano, D
JournalProc Natl Acad Sci U S A
Date Published1996 Apr 2
KeywordsAmino Acid Sequence, Binding Sites, Clostridium, Crystallography, X-Ray, Escherichia coli, Macromolecular Substances, Models, Molecular, Models, Structural, Molecular Sequence Data, Protein Folding, Protein Structure, Secondary, Pyruvate, Orthophosphate Dikinase, Recombinant Proteins, Software

The crystal structure of pyruvate phosphate dikinase, a histidyl multiphosphotransfer enzyme that synthesizes adenosine triphosphate, reveals a three-domain molecule in which the phosphohistidine domain is flanked by the nucleotide and the phosphoenolpyruvate/pyruvate domains, with the two substrate binding sites approximately 45 angstroms apart. The modes of substrate binding have been deduced by analogy to D-Ala-D-Ala ligase and to pyruvate kinase. Coupling between the two remote active sites is facilitated by two conformational states of the phosphohistidine domain. While the crystal structure represents the state of interaction with the nucleotide, the second state is achieved by swiveling around two flexible peptide linkers. This dramatic conformational transition brings the phosphocarrier residue in close proximity to phosphoenolpyruvate/pyruvate. The swiveling-domain paradigm provides an effective mechanism for communication in complex multidomain/multiactive site proteins.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID8610096
PubMed Central IDPMC39685
Grant ListGM36260 / GM / NIGMS NIH HHS / United States