1qnt
From Proteopedia
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- | [[Image:1qnt.gif|left|200px]]<br /> | + | [[Image:1qnt.gif|left|200px]]<br /><applet load="1qnt" size="450" color="white" frame="true" align="right" spinBox="true" |
- | <applet load="1qnt" size="450" color="white" frame="true" align="right" spinBox="true" | + | |
caption="1qnt, resolution 1.90Å" /> | caption="1qnt, resolution 1.90Å" /> | ||
'''X-RAY STRUCTURE OF HUMAN O6ALKYLGUANINE-DNA ALKYLTRANSFERASE'''<br /> | '''X-RAY STRUCTURE OF HUMAN O6ALKYLGUANINE-DNA ALKYLTRANSFERASE'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
- | 1QNT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Methylated-DNA--[protein]-cysteine_S-methyltransferase Methylated-DNA--[protein]-cysteine S-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.63 2.1.1.63] | + | 1QNT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Methylated-DNA--[protein]-cysteine_S-methyltransferase Methylated-DNA--[protein]-cysteine S-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.63 2.1.1.63] Known structural/functional Site: <scene name='pdbsite=ACC:Alkyl Acceptor'>ACC</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1QNT OCA]. |
==Reference== | ==Reference== | ||
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[[Category: methyltransferase]] | [[Category: methyltransferase]] | ||
- | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 17:58:04 2007'' |
Revision as of 15:48, 18 December 2007
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X-RAY STRUCTURE OF HUMAN O6ALKYLGUANINE-DNA ALKYLTRANSFERASE
Overview
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.
About this Structure
1QNT is a Single protein structure of sequence from Homo sapiens. Active as [protein-cysteine_S-methyltransferase Methylated-DNA--[protein]-cysteine S-methyltransferase], with EC number 2.1.1.63 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
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[[Category: Methylated-DNA--[protein]-cysteine S-methyltransferase]]
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