Structure of the O-acetylserine sulfhydrylase isoenzyme CysM from Escherichia coli.
The enzyme O-acetylserine sulfhydrylase participates in the biosynthesis of l-cysteine in bacteria and plants. The structure of isoenzyme B (CysM) from Escherichia coli was established in a hexagonal crystal form at 2.7 A resolution (wild-type) and in a merohedrally twinned tetragonal crystal form at 2.1 A resolution (surface mutant). Structural superpositions revealed the variations with respect to isoenzyme A (CysK) and explained the different substrate specificities. A geometric model of the reaction catalyzed by CysM is proposed. Both isoenzymes are used for the production of l-amino acid derivatives as building blocks for the synthesis of peptides and peptidomimetic drugs. Since the structure of CysM revealed a remarkable main chain variation at the active center, it constitutes a further starting point for engineering mutants with novel substrate specificities.
Claus
Michael T
MT
Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität, Albertstrasse 21, D-79104 Freiburg im Breisgau, Germany.
Zocher
Georg E
GE
Maier
Thomas H P
TH
Schulz
Georg E
GE
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D003547:Cysteine Synthase / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D019281:Dimerization; D004926:Escherichia coli / Q000201:enzymology*; D007527:Isoenzymes / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D012486:Salmonella typhimurium / Q000201:enzymology; D017386:Sequence Homology, Amino Acid
D007527:Isoenzymes; D011994:Recombinant Proteins; D003547:Cysteine Synthase