1njb
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THYMIDYLATE SYNTHASE
OverviewOverview
Thymidylate synthase (TS) methylates only dUMP, not dCMP. The crystal, structure of TS.dCMP shows sCMP 4-NH2 excluded from the space between, Asn-229 and His-199 by the hydrogen bonding and steric properties and, Asn-229. Consequently, 6-C of dCMP is over 4 A from the active site, sulfhydryl. The Asn-229 side chain is prevented from flipping 180 degrees, to and orientation the could hydrogen bond to dCMP by a hydrogen bond, network between conserved residues. Thus, the specific binding of dUMP by, TS results from occlusion of competing substrates by steric and electronic, effects of residues in the active site cavity. When Asn-229 is replaced by, a cysteine, the Cys-229 S gamma rotates out of the active site, and the, mutant enzyme binds both dCMP and dUMP tightly but does not methylate, ... [(full description)]
About this StructureAbout this Structure
1NJB is a [Single protein] structure of sequence from [Lactobacillus casei] with UMP as [ligand]. Active as [Thymidylate synthase], with EC number [2.1.1.45]. Structure known Active Site: CAT. Full crystallographic information is available from [OCA].
ReferenceReference
Partitioning roles of side chains in affinity, orientation, and catalysis with structures for mutant complexes: asparagine-229 in thymidylate synthase., Finer-Moore JS, Liu L, Schafmeister CE, Birdsall DL, Mau T, Santi DV, Stroud RM, Biochemistry. 1996 Apr 23;35(16):5125-36. PMID:8611496
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