220.127.116.11 - Cystathionine gamma-synthase
- O-succinylhomoserine synthetase.
- O-succinylhomoserine (thiol)-lyase.
- O-succinyl-L-homoserine succinate-lyase (adding cysteine).
- Homoserine transsuccinylase.
- Cystathionine synthase.
- O-succinylhomoserine synthase.
- Cystathionine synthetase.
L-cysteine + O-succinyl-L-homoserine = H(+) + L,L-cystathionine + succinate
- Step 1
- Step 2
- Step 3
- Step 4
- Step 5
- Step 6
- Step 7
- Step 8
- Step 9
- Step 10
- Step 11
- Step 12
- Step 13
- Transaldimination: (i) OSHS binds through Arg 48*, Tyr 101 and Arg 361. (ii) The alpha-amino group of the substrate must be deprotonated for nucleophilic attack on C4' of the internal aldimine. Tyr 101 exists as phenolate due to two neighbouring positive charges (Arg 48* and NH of the internal aldimine). Therefore, Tyr 101 abstracts a proton from the incoming substrate and initiates transaldimination.
- Generation of the ketimine intermediate: (i) Lys 198 is responsible for proton transfer from the alpha-C to C4' of the PLP cofactor. The protonated amino group of Lys 198 is guided into a favourable position near C4' by Tyr 46*. After alpha-C deprotonation, a quinonoid intermediate is formed, which is stabilised by stacking interactions with Tyr 101. (ii) The Lys 198 e-amino group is positively charged and is therefore attracted to the negatively charged phosphate group of the PLP cofactor, orientating it into a favourable position for bond cleavage. (iii) Due to the new positioning of Lys 198, this residue is able to abstract a proton from the beta-C to initiate gamma-cleavage.
- Release of succinate Tyr 101 facilitates the release of succinate by and acid/base mechanism. The resulting beta-gamma unsaturated ketimine exhibits pronounced electron deficiency, caused by the protonated Schiff base, leading to activation of gamma-C towards Michael nucleophilic addition by L-cysteinate.
- Transaldimination: the reverse steps of 1-3 occur (beta-C protonation, C4' deprotonation, alpha-C protonation.)
|AA||Uniprot||Uniprot Resid||PDB||PDB Resid|
overall reactant used, proton transfer, unimolecular elimination by the conjugate base, overall product formed, enzyme-substrate complex formation, bimolecular nucleophilic addition, michael addition, native state of cofactor regenerated, intermediate formation, intermediate terminated, native state of enzyme regenerated, bimolecular electrophilic addition, cofactor used, intermediate collapse, enzyme-substrate complex cleavage
There are no kinetic parameters information for this Enzyme
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- Metabolic control analysis of the transsulfuration pathway and the compensatory role of the cysteine transport in Trypanosoma cruzi.
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- Hydrogen sulfide promotes migration of trophoblast cells by a Rho GTPase mediated actin cytoskeleton reorganization.
- Sulfur-Element containing metabolic pathways in human health and crosstalk with the microbiome.
- Cystathionine gamma-synthase is essential for methionine biosynthesis in Fusarium graminearum.