Allosterically gated enzyme dynamics in the cysteine synthase complex regulate cysteine biosynthesis in Arabidopsis thaliana.
Plants and bacteria assimilate sulfur into cysteine. Cysteine biosynthesis involves a bienzyme complex, the cysteine synthase complex (CSC), which consists of serine-acetyl-transferase (SAT) and O-acetyl-serine-(thiol)-lyase (OAS-TL) enzymes. The activity of OAS-TL is reduced by formation of the CSC. Although this reduction is an inherent part of the self-regulation cycle of cysteine biosynthesis, there has until now been no explanation as to how OAS-TL loses activity in plants. Complexation of SAT and OAS-TL involves binding of the C-terminal tail of SAT in one of the active sites of the homodimeric OAS-TL. We here explore the flexibility of the unoccupied active site in Arabidopsis thaliana cytosolic and mitochondrial OAS-TLs. Our results reveal two gates in the OAS-TL active site that define its accessibility. The observed dynamics of the gates show allosteric closure of the unoccupied active site of OAS-TL in the CSC, which can hinder substrate binding, abolishing its turnover to cysteine.
Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies (HITS), 69118 Heidelberg, Germany.
Anna
A
Feldman-Salit
Markus
M
Wirtz
Esther D
ED
Lenherr
Christian
C
Throm
Michael
M
Hothorn
Klaus
K
Scheffzek
Rüdiger
R
Hell
Rebecca C
RC
Wade
D000494:Allosteric Regulation; D020816:Amino Acid Motifs; D017360:Arabidopsis / Q000201:enzymology*; D029681:Arabidopsis Proteins / Q000737:chemistry*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000096:biosynthesis*; D003547:Cysteine Synthase / Q000737:chemistry*; D008928:Mitochondria / Q000201:enzymology*; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D051050:Serine O-Acetyltransferase / Q000737:chemistry
D029681:Arabidopsis Proteins; D010446:Peptide Fragments; D051050:Serine O-Acetyltransferase; D003547:Cysteine Synthase; D003545:Cysteine