Substrate-induced asymmetry and channel closure revealed by the apoenzyme structure of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase

Van K. Morris, Tina Izard

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Phosphopantetheine adenylyltransferase (PPAT) catalyzes the penultimate step in prokaryotic coenzyme A (CoA) biosynthesis, directing the transfer of an adenylyl group from ATP to 4′-phosphopantetheine (Ppant) to yield dephospho-CoA (dPCoA). The crystal structures of Escherichia coli PPAT bound to its substrates, product, and inhibitor revealed an allosteric hexameric enzyme with half-of-sites reactivity, and established an in-line displacement catalytic mechanism. To provide insight into the mechanism of ligand binding we solved the apoenzyme (Apo) crystal structure of PPAT from Mycobacterium tuberculosis. In its Apo form, PPAT is a symmetric hexamer with an open solvent channel. However, ligand binding provokes asymmetry and alters the structure of the solvent channel, so that ligand binding becomes restricted to one trimer.

Original languageEnglish (US)
Pages (from-to)2547-2552
Number of pages6
JournalProtein Science
Volume13
Issue number9
DOIs
StatePublished - Sep 1 2004

Keywords

  • Apoenzyme
  • Coenzyme A
  • Phosphopantetheine adenylyltransferase
  • Tuberculosis
  • X-ray structure

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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