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| | <StructureSection load='1cet' size='340' side='right'caption='[[1cet]], [[Resolution|resolution]] 2.05Å' scene=''> | | <StructureSection load='1cet' size='340' side='right'caption='[[1cet]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1cet]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Plafa Plafa]. The June 2008 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Lactate Dehydrogenase'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2008_6 10.2210/rcsb_pdb/mom_2008_6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CET OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1CET FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1cet]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plafa Plafa]. The June 2008 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Lactate Dehydrogenase'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2008_6 10.2210/rcsb_pdb/mom_2008_6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CET OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CET FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CLQ:N4-(7-CHLORO-QUINOLIN-4-YL)-N1,N1-DIETHYL-PENTANE-1,4-DIAMINE'>CLQ</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLQ:N4-(7-CHLORO-QUINOLIN-4-YL)-N1,N1-DIETHYL-PENTANE-1,4-DIAMINE'>CLQ</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/L-lactate_dehydrogenase L-lactate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.27 1.1.1.27] </span></td></tr> | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/L-lactate_dehydrogenase L-lactate dehydrogenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.27 1.1.1.27] </span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1cet FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cet OCA], [http://pdbe.org/1cet PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1cet RCSB], [http://www.ebi.ac.uk/pdbsum/1cet PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1cet ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1cet FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cet OCA], [https://pdbe.org/1cet PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cet RCSB], [https://www.ebi.ac.uk/pdbsum/1cet PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cet ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
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| | ==See Also== | | ==See Also== |
| - | *[[Lactate Dehydrogenase|Lactate Dehydrogenase]] | + | *[[Lactate dehydrogenase 3D structures|Lactate dehydrogenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Structural highlights
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Although the molecular mechanism by which chloroquine exerts its effects on the malarial parasite Plasmodium falciparum remains unclear, the drug has previously been found to interact specifically with the glycolytic enzyme lactate dehydrogenase from the parasite. In this study we have determined the crystal structure of the complex between chloroquine and P. falciparum lactate dehydrogenase. The bound chloroquine is clearly seen within the NADH binding pocket of the enzyme, occupying a position similar to that of the adenyl ring of the cofactor. Chloroquine hence competes with NADH for binding to the enzyme, acting as a competitive inhibitor for this critical glycolytic enzyme. Specific interactions between the drug and amino acids unique to the malarial form of the enzyme suggest this binding is selective. Inhibition studies confirm that chloroquine acts as a weak inhibitor of lactate dehydrogenase, with mild selectivity for the parasite enzyme. As chloroquine has been shown to accumulate to millimolar concentrations within the food vacuole in the gut of the parasite, even low levels of inhibition may contribute to the biological efficacy of the drug. The structure of this enzyme-inhibitor complex provides a template from which the quinoline moiety might be modified to develop more efficient inhibitors of the enzyme.
Chloroquine binds in the cofactor binding site of Plasmodium falciparum lactate dehydrogenase.,Read JA, Wilkinson KW, Tranter R, Sessions RB, Brady RL J Biol Chem. 1999 Apr 9;274(15):10213-8. PMID:10187806[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Read JA, Wilkinson KW, Tranter R, Sessions RB, Brady RL. Chloroquine binds in the cofactor binding site of Plasmodium falciparum lactate dehydrogenase. J Biol Chem. 1999 Apr 9;274(15):10213-8. PMID:10187806
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