2bzg
From Proteopedia
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|GENE= | |GENE= | ||
|DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam05724 TPMT]</span> | |DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam05724 TPMT]</span> | ||
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2bzg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bzg OCA], [http://www.ebi.ac.uk/pdbsum/2bzg PDBsum | + | |RELATEDENTRY= |
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2bzg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bzg OCA], [http://www.ebi.ac.uk/pdbsum/2bzg PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2bzg RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
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| - | ==Disease== | ||
| - | Known disease associated with this structure: 6-mercaptopurine sensitivity OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=187680 187680]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:14:06 2008'' |
Revision as of 23:14, 30 March 2008
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| , resolution 1.58Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , | ||||||
| Activity: | Thiopurine S-methyltransferase, with EC number 2.1.1.67 | ||||||
| Domains: | TPMT | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF THIOPURINE S-METHYLTRANSFERASE.
Overview
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.
About this Structure
2BZG is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Mon Mar 31 02:14:06 2008
Categories: Homo sapiens | Single protein | Thiopurine S-methyltransferase | Arrowsmith, C H. | Battaile, K P. | Bochkarev, A. | Dong, A. | Edwards, A M. | Loppnau, P. | Plotnikov, A N. | Sgc, Structural Genomics Consortium. | Sundstrom, M. | Weigelt, J. | Wu, H. | Zeng, H. | Methyltransferase | Polymorphism | Protein structure initiative | Psi | Structural genomics consortium (sgc) | Transferase
