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1qnt
From Proteopedia
| 1qnt, resolution 1.90Å () | |||||||||
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| Activity: | [protein-cysteine_S-methyltransferase Methylated-DNA--[protein]-cysteine S-methyltransferase], with EC number 2.1.1.63 | ||||||||
| Related: | 1sfe | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
X-RAY STRUCTURE OF HUMAN O6ALKYLGUANINE-DNA ALKYLTRANSFERASE
The mutagenic and carcinogenic effects of simple alkylating agents are mainly due to O(6)-alkylation of guanine in DNA. This lesion results in transition mutations. In both prokaryotic and eukaryotic cells, repair is effected by direct reversal of the damage by a suicide protein, O(6)-alkylguanine-DNA alkyltransferase. The alkyltransferase removes the alkyl group to one of its own cysteine residues. However, this mechanism for preserving genomic integrity limits the effectiveness of certain alkylating anticancer agents. A high level of the alkyltransferase in many tumour cells renders them resistant to such drugs. Here we report the X-ray structure of the human alkyltransferase solved using the technique of multiple wavelength anomalous dispersion. This structure explains the markedly different specificities towards various O(6)-alkyl lesions and inhibitors when compared with the Escherichia coli protein (for which the structure has already been determined). It is also used to interpret the behaviour of certain mutant alkyltransferases to enhance biochemical understanding of the protein. Further examination of the various models proposed for DNA binding is also permitted. This structure may be useful for the design and refinement of drugs as chemoenhancers of alkylating agent chemotherapy.
Crystal structure of the human O(6)-alkylguanine-DNA alkyltransferase., Wibley JE, Pegg AE, Moody PC, Nucleic Acids Res. 2000 Jan 15;28(2):393-401. PMID:10606635
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1qnt is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Wibley JE, Pegg AE, Moody PC. Crystal structure of the human O(6)-alkylguanine-DNA alkyltransferase. Nucleic Acids Res. 2000 Jan 15;28(2):393-401. PMID:10606635
- Moore MH, Gulbis JM, Dodson EJ, Demple B, Moody PC. Crystal structure of a suicidal DNA repair protein: the Ada O6-methylguanine-DNA methyltransferase from E. coli. EMBO J. 1994 Apr 1;13(7):1495-501. PMID:8156986
- Wibley JE, McKie JH, Embrey K, Marks DS, Douglas KT, Moore MH, Moody PC. A homology model of the three-dimensional structure of human O6-alkylguanine-DNA alkyltransferase based on the crystal structure of the C-terminal domain of the Ada protein from Escherichia coli. Anticancer Drug Des. 1995 Jan;10(1):75-95. PMID:7695814
