Structure of serine acetyltransferase in complexes with CoA and its cysteine feedback inhibitor

Laurence R. Olsen, Bin Huang, Matthew W. Vetting, Steven L. Roderick

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Serine acetyltransferase (SAT, EC 2.3.1.30) catalyzes the CoA-dependent acetylation of the side chain hydroxyl group of L-serine to form O-acetylserine, as the first step of a two-step biosynthetic pathway in bacteria and plants leading to the formation of L-cysteine. This reaction represents a key metabolic point of regulation for the cysteine biosynthetic pathway due to its feedback inhibition by cysteine. We have determined the X-ray crystal structure of Haemophilus influenzae SAT in complexes with CoA and its cysteine feedback inhibitor. The enzyme is a 175 kDa hexamer displaying the characteristic left-handed parallel β-helix (LβH) structural domain of the hexapeptide acyltransferase superfamily of enzymes. Cysteine is bound in a crevice between adjacent LβH domains and underneath a loop excluded from the coiled LβH. The proximity of its thiol group to the thiol group of CoA derived from superimposed models of the cysteine and CoA complexes confirms that cysteine is bound at the active site. Analysis of the contacts of SAT with cysteine and CoA and the conformational differences that distinguish these complexes provides a structural basis for cysteine feedback inhibition, which invokes competition between cysteine and serine binding and a cysteine-induced conformational change of the C-terminal segment of the enzyme that excludes binding of the cofactor.

Original languageEnglish (US)
Pages (from-to)6013-6019
Number of pages7
JournalBiochemistry
Volume43
Issue number20
DOIs
StatePublished - May 25 2004

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Serine O-Acetyltransferase
Coenzyme A
Cysteine
Feedback
Biosynthetic Pathways
Sulfhydryl Compounds
Serine
Enzymes
Acyltransferases
Acetylation
Haemophilus influenzae

ASJC Scopus subject areas

  • Biochemistry

Cite this

Structure of serine acetyltransferase in complexes with CoA and its cysteine feedback inhibitor. / Olsen, Laurence R.; Huang, Bin; Vetting, Matthew W.; Roderick, Steven L.

In: Biochemistry, Vol. 43, No. 20, 25.05.2004, p. 6013-6019.

Research output: Contribution to journalArticle

Olsen, Laurence R. ; Huang, Bin ; Vetting, Matthew W. ; Roderick, Steven L. / Structure of serine acetyltransferase in complexes with CoA and its cysteine feedback inhibitor. In: Biochemistry. 2004 ; Vol. 43, No. 20. pp. 6013-6019.
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