1bkp
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THERMOSTABLE THYMIDYLATE SYNTHASE A FROM BACILLUS SUBTILIS
OverviewOverview
Unlike all other organisms studied to date, Bacillus subtilis expresses, two different thymidylate synthases: bsTS-A and bsTS-B. bsTS-A displays, enhanced enzymatic and structural thermal stability uncharacteristic of, most TSs. Despite the high level of TS conservation across most species, bsTS-A shares low sequence identity (<40%) with the majority of TSs from, other organisms. This TS and the TSs from Lactococcus lactis and phage, Phi3T-to which it is most similar-have been of interest for some time, since, by structure-based sequence alignment, they appear to lack several, key residues shown by mutagenesis to be essential to enzymatic function, [Greene, P. J., Yu, P. L., Zhao, J., Schiffer, C. A., and Santi, D. (1994), Protein Sci. 3, 1114-6]. In addition, bsTS-A demonstrates specific, activity 2-3-fold higher than TS from Lactobacillus casei or Escherichia, coli. We have solved the crystal structure of this unusual TS in four, crystal forms to a maximum resolution of 1.7 A. Each of these crystal, forms contains either one or two noncrystallographically related dimers., Stabilization of the beta-sheet dimer interface through a dramatic, architecture of buttressed internal salt bridges maintains the structural, integrity of bsTS-A at elevated temperatures. Melting curves of TSs from, L. casei and E. coli are compared to that of TS-A from B. subtilis and, correlated with numbers of hydrogen bonds, salt bridges, and the numbers, of interactions localized to the dimer interface. Analysis of this, structure will shed light on the conservation of function across diversity, of sequence, as well as provide insights into the thermal stabilization of, a highly conserved enzyme.
About this StructureAbout this Structure
1BKP is a Single protein structure of sequence from Bacillus subtilis. Active as Thymidylate synthase, with EC number 2.1.1.45 Structure known Active Sites: CAA and CAB. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of a unique thermal-stable thymidylate synthase from Bacillus subtilis., Stout TJ, Schellenberger U, Santi DV, Stroud RM, Biochemistry. 1998 Oct 20;37(42):14736-47. PMID:9778348
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