Determinants of enzymatic specificity in the cys-met-metabolism PLP-dependent enzyme family: crystal structure of cystathionine γ-lyase from yeast and intrafamiliar structure comparison

Messerschmidt, A., Worbs, M., Steegborn, C., Wahl, M.C., Huber, Robert, Laber, B. and Clausen, T. 2003. Determinants of enzymatic specificity in the cys-met-metabolism PLP-dependent enzyme family: crystal structure of cystathionine γ-lyase from yeast and intrafamiliar structure comparison. Biological Chemistry 384 (3) , pp. 373-386. 10.1515/BC.2003.043

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Abstract

The crystal structure of cystathionine γ-lyase (CGL) from yeast has been solved by molecular replacement at a resolution of 2.6 å. The molecule consists of 393 amino acid residues and one PLP moiety and is arranged in the crystal as a tetramer with D2 symmetry as in other related enzymes of the CysMetmetabolism PLP-dependent family like cystathionine β-lyase (CBL). A structure comparison with other family members revealed surprising insights into the tuning of enzymatic specificity between the different family members. CGLs from yeast or human are virtually identical at their active sites to cystathionine γ-synthase (CGS) from E. coli. Both CGLs and bacterial CGSs exhibit γ-synthase and γ-lyase activities depending on their position in the metabolic pathway and the available substrates. This group of enzymes has a glutamate (E333 in yeast CGL) which binds to the distal group of cystathionine (CTT) or the amino group of cysteine. Plant CGSs use homoserine phosphate instead of O-succinyl-homoserine as one substrate. This is reflected by a partially different active site structure in plant CGSs. In CGL and CBL the pseudosymmetric substrate must dock at the active site in different orientations, with S in γ-position (CBL) or in δ-position (CGL). The conserved glutamate steers the substrate as seen in other CGLs. In CBLs this position is occupied by either tyrosine or hydrophobic residues directing binding of CTT such that S is in the in γ-position. In methionine γ-lyase a hydrophic patch operates as recognition site for the methyl group of the methionine substrate.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Biosciences
Subjects:	Q Science > QR Microbiology
Publisher:	de Gruyter
ISSN:	1431-6730
Last Modified:	24 Jun 2017 11:00
URI:	https://orca.cardiff.ac.uk/id/eprint/70204

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