2h11

Amino-terminal Truncated Thiopurine S-Methyltransferase Complexed with S-Adenosyl-L-Homocysteine

spinqualitylabelsall models 2h11, resolution 1.89Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2h11 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.89Å Ligands: B3P, SAH, SCN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease TPMT_HUMAN Defects in TPMT are the cause of thiopurine S-methyltransferase deficiency (TPMT deficiency) [MIM:610460. TPMT is an enzyme involved in the normal metabolic inactivation of thiopurine drugs. These drugs are generally used as immunosupressants or cytotoxic drugs and are prescribed for a variety of clinical conditions including leukemia, autoimmune disease and organ transplantation. Patients with intermediate or no TPMT activity are at risk of toxicity after receiving standard doses of thiopurine drugs and it is shown that inter-individual differences in response to these drugs are largely determined by genetic variation at the TPMT locus. Function TPMT_HUMAN Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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