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Ligand binding induces a large conformational change in O-acetylserine sulfhydrylase from Salmonella typhimurium.

Burkhard P, Tai CH, Ristroph CM, Cook PF, Jansonius JN
J Mol Biol 291 941-53 (1999)
Cited: 70 times
EuropePMC logo PMID: 10452898

Abstract

Covalent binding of L-methionine as an external aldimine to the pyridoxal 5'-phosphate-cofactor in the K41A mutant of O-acetylserine sulfhydrylase from Salmonella typhimurium induces a large conformational change in the protein. Methionine mimics the action of the substrate O-acetyl-L-serine during catalysis. The alpha-carboxylate moiety of L-methionine in external aldimine linkage with the active site pyridoxal 5'-phosphate forms a hydrogen bonding network to the "asparagine-loop" P67-T68-N69-G70 which adopts a different conformation than in the native protein. The side-chain nitrogen of Asn69 moves more than 7 A to make a hydrogen bond to the alpha-carboxylate group of the inhibitor. As the external aldimine is formed, the PLP tilts by 13 degrees along its longitudinal axis such that C4' moves toward the entrance to the active site and the side-chain of the methionine is directed toward the active site entrance. The local rearrangement acts as a trigger to induce a large global conformational change in the protein. A subdomain comprised of beta-strand 4, alpha-helix 3, beta-strand 5 and alpha-helix 4 moves towards the active site by a rotation of 7 degrees. This subdomain movement results in a reduction of the severe twist of its central beta-sheet and reduces the active site entrance to a small hole, giving access only to small molecules like sulfide, the second substrate, or acetate, the first product.

Reviews - 1d6s mentioned but not cited (1)

  1. Insights into multifaceted activities of CysK for therapeutic interventions. Joshi P, Gupta A, Gupta V. 3 Biotech 9 44 (2019)

Articles - 1d6s mentioned but not cited (3)

  1. Crystallization and preliminary crystallographic analysis of cysteine synthase from Entamoeba histolytica. Krishna C, Jain R, Kashav T, Wadhwa D, Alam N, Gourinath S. Acta Crystallogr Sect F Struct Biol Cryst Commun 63 512-515 (2007)
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  3. Revealing the Dynamic Allosteric Changes Required for Formation of the Cysteine Synthase Complex by Hydrogen-Deuterium Exchange MS. Rosa B, Dickinson ER, Marchetti M, Campanini B, Pioselli B, Bettati S, Rand KD. Mol Cell Proteomics 20 100098 (2021)


Reviews citing this publication (7)

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Related citations provided by authors (1)

  1. Three-dimensional Structure of O-Acetylserine Sulfhydrylase from Salmonella typhimurium. Burkhard P, Rao GS, Hohenester E, Schnackerz KD, Cook PF, Jansonius JN J. Mol. Biol. 283 121-133 (1998)

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