1CS1

CYSTATHIONINE GAMMA-SYNTHASE (CGS) FROM ESCHERICHIA COLI

Summary for 1CS1

• Entry DOI: 10.2210/pdb1cs1/pdb
• Descriptor: PROTEIN (CYSTATHIONINE GAMMA-SYNTHASE), 2,4-DIOXO-PENTANEDIOIC ACID (3 entities in total)
• Functional Keywords: lyase, llp-dependent enzymes, methionine biosynthesis
• Biological source: Escherichia coli
• Total number of polymer chains: 4
• Total formula weight: 167461.74

Authors

Clausen, T.,Messerschmidt, A. (deposition date: 1998-09-23, release date: 1999-09-27, Last modification date: 2023-11-15)

Primary citation

Clausen, T.,Huber, R.,Prade, L.,Wahl, M.C.,Messerschmidt, A.
Crystal structure of Escherichia coli cystathionine gamma-synthase at 1.5 A resolution.
EMBO J., 17:6827-6838, 1998

PubMed Abstract: The transsulfuration enzyme cystathionine gamma-synthase (CGS) catalyses the pyridoxal 5'-phosphate (PLP)-dependent gamma-replacement of O-succinyl-L-homoserine and L-cysteine, yielding L-cystathionine. The crystal structure of the Escherichia coli enzyme has been solved by molecular replacement with the known structure of cystathionine beta-lyase (CBL), and refined at 1.5 A resolution to a crystallographic R-factor of 20.0%. The enzyme crystallizes as an alpha4 tetramer with the subunits related by non-crystallographic 222 symmetry. The spatial fold of the subunits, with three functionally distinct domains and their quaternary arrangement, is similar to that of CBL. Previously proposed reaction mechanisms for CGS can be checked against the structural model, allowing interpretation of the catalytic and substrate-binding functions of individual active site residues. Enzyme-substrate models pinpoint specific residues responsible for the substrate specificity, in agreement with structural comparisons with CBL. Both steric and electrostatic designs of the active site seem to achieve proper substrate selection and productive orientation. Amino acid sequence and structural alignments of CGS and CBL suggest that differences in the substrate-binding characteristics are responsible for the different reaction chemistries. Because CGS catalyses the only known PLP-dependent replacement reaction at Cgamma of certain amino acids, the results will help in our understanding of the chemical versatility of PLP.

PubMed: 9843488
DOI: 10.1093/emboj/17.23.6827

Experimental method

X-RAY DIFFRACTION (1.5 Å)