2bzg
CRYSTAL STRUCTURE OF THIOPURINE S-METHYLTRANSFERASE.
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OverviewOverview
Human thiopurine S-methyltransferase (TPMT) exhibits considerable, person-to-person variation in activity to thiopurine drugs. We have, produced an N-terminal truncation of human TPMT protein, crystallized the, protein in complex with the methyl donor product, S-adenosyl-L-homocysteine, and determined the atomic structure to the, resolution of 1.58 and 1.89 A, respectively, for the seleno-methionine, incorporated and wild type proteins. The structure of TPMT indicates that, the naturally occurring amino acid polymorphisms scatter throughout the, structure, and that the amino acids whose alteration have the most, influence on function are those that form intra-molecular stabilizing, interactions (mainly van der Waals contacts). Furthermore, we have, produced four TPMT mutant proteins containing variant alleles of TPMT*2, *3A, *3B, and *3C and examined the structure-function relationship of the, mutant proteins based on their expression and solubility in bacteria and, their thermostability profile.
DiseaseDisease
Known disease associated with this structure: 6-mercaptopurine sensitivity OMIM:[187680]
About this StructureAbout this Structure
2BZG is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Thiopurine S-methyltransferase, with EC number 2.1.1.67 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Structural basis of allele variation of human thiopurine-S-methyltransferase., Wu H, Horton JR, Battaile K, Allali-Hassani A, Martin F, Zeng H, Loppnau P, Vedadi M, Bochkarev A, Plotnikov AN, Cheng X, Proteins. 2007 Apr 1;67(1):198-208. PMID:17243178
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