1kmv: Difference between revisions
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New page: left|200px<br /> <applet load="1kmv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kmv, resolution 1.05Å" /> '''HUMAN DIHYDROFOLATE... |
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[[Image:1kmv.gif|left|200px]]<br /> | [[Image:1kmv.gif|left|200px]]<br /><applet load="1kmv" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1kmv" size=" | |||
caption="1kmv, resolution 1.05Å" /> | caption="1kmv, resolution 1.05Å" /> | ||
'''HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND (Z)-6-(2-[2,5-DIMETHOXYPHENYL]ETHEN-1-YL)-2,4-DIAMINO-5-METHYLPYRIDO[2,3-D]PYRIMIDINE (SRI-9662), A LIPOPHILIC ANTIFOLATE'''<br /> | '''HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND (Z)-6-(2-[2,5-DIMETHOXYPHENYL]ETHEN-1-YL)-2,4-DIAMINO-5-METHYLPYRIDO[2,3-D]PYRIMIDINE (SRI-9662), A LIPOPHILIC ANTIFOLATE'''<br /> | ||
==Overview== | ==Overview== | ||
The crystal structures of two human dihydrofolate reductase (hDHFR) | The crystal structures of two human dihydrofolate reductase (hDHFR) ternary complexes, each with bound NADPH cofactor and a lipophilic antifolate inhibitor, have been determined at atomic resolution. The potent inhibitors 6-([5-quinolylamino]methyl)-2,4-diamino-5-methylpyrido[2,3-d]pyrimidine (SRI-9439) and (Z)-6-(2-[2,5-dimethoxyphenyl]ethen-1-yl)-2,4-diamino-5-methylpyrido[2,3-d ]pyrimidine (SRI-9662) were developed at Southern Research Institute against Toxoplasma gondii DHFR-thymidylate synthase. The 5-deazapteridine ring of each inhibitor adopts an unusual puckered conformation that enables the formation of identical contacts in the active site. Conversely, the quinoline and dimethoxybenzene moieties exhibit distinct binding characteristics that account for the differences in inhibitory activity. In both structures, a salt-bridge is formed between Arg70 in the active site and Glu44 from a symmetry-related molecule in the crystal lattice that mimics the binding of methotrexate to DHFR. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1KMV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4, LII, NDP and DMS as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] Full crystallographic information is available from [http:// | 1KMV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=LII:'>LII</scene>, <scene name='pdbligand=NDP:'>NDP</scene> and <scene name='pdbligand=DMS:'>DMS</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KMV OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Borhani, D | [[Category: Borhani, D W.]] | ||
[[Category: Heroux, A.]] | [[Category: Heroux, A.]] | ||
[[Category: Johnson, C | [[Category: Johnson, C A.]] | ||
[[Category: Klon, A | [[Category: Klon, A E.]] | ||
[[Category: Pathak, V.]] | [[Category: Pathak, V.]] | ||
[[Category: Piper, J | [[Category: Piper, J R.]] | ||
[[Category: Ross, L | [[Category: Ross, L J.]] | ||
[[Category: DMS]] | [[Category: DMS]] | ||
[[Category: LII]] | [[Category: LII]] | ||
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[[Category: reductase]] | [[Category: reductase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:35:51 2008'' | ||
