2H11

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

Summary for 2H11

• Entry DOI: 10.2210/pdb2h11/pdb
• Descriptor: Thiopurine S-methyltransferase, THIOCYANATE ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (5 entities in total)
• Functional Keywords: binary protein-cofactor complex, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 55141.47

Authors

Horton, J.R.,Cheng, X. (deposition date: 2006-05-15, release date: 2006-11-21, Last modification date: 2023-08-30)

Primary citation

Wu, H.,Horton, J.R.,Battaile, K.,Allali-Hassani, A.,Martin, F.,Zeng, H.,Loppnau, P.,Vedadi, M.,Bochkarev, A.,Plotnikov, A.N.,Cheng, X.
Structural basis of allele variation of human thiopurine-S-methyltransferase.
Proteins, 67:198-208, 2007

PubMed Abstract: 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.

PubMed: 17243178
DOI: 10.1002/prot.21272

Experimental method

X-RAY DIFFRACTION (1.89 Å)