4l4s: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4l4s]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L4S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4L4S FirstGlance]. <br> | <table><tr><td colspan='2'>[[4l4s]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L4S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4L4S FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4l4r|4l4r]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4l4r|4l4r]]</td></tr> | ||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LDHA, PIG19 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LDHA, PIG19 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr><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'>[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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4l4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l4s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4l4s RCSB], [http://www.ebi.ac.uk/pdbsum/4l4s PDBsum]</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=4l4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l4s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4l4s RCSB], [http://www.ebi.ac.uk/pdbsum/4l4s PDBsum]</span></td></tr> | ||
<table> | </table> | ||
== Disease == | == Disease == | ||
[[http://www.uniprot.org/uniprot/LDHA_HUMAN LDHA_HUMAN]] Defects in LDHA are the cause of glycogen storage disease type 11 (GSD11) [MIM:[http://omim.org/entry/612933 612933]]. A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue.<ref>PMID:2334430</ref> | [[http://www.uniprot.org/uniprot/LDHA_HUMAN LDHA_HUMAN]] Defects in LDHA are the cause of glycogen storage disease type 11 (GSD11) [MIM:[http://omim.org/entry/612933 612933]]. A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue.<ref>PMID:2334430</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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Structural characterization of the apo form and NADH binary complex of human lactate dehydrogenase.,Dempster S, Harper S, Moses JE, Dreveny I Acta Crystallogr D Biol Crystallogr. 2014 May;70(Pt 5):1484-90. doi:, 10.1107/S1399004714005422. Epub 2014 Apr 30. PMID:24816116<ref>PMID:24816116</ref> | Structural characterization of the apo form and NADH binary complex of human lactate dehydrogenase.,Dempster S, Harper S, Moses JE, Dreveny I Acta Crystallogr D Biol Crystallogr. 2014 May;70(Pt 5):1484-90. doi:, 10.1107/S1399004714005422. Epub 2014 Apr 30. PMID:24816116<ref>PMID:24816116</ref> | ||
From | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
== References == | == References == | ||
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[[Category: Human]] | [[Category: Human]] | ||
[[Category: L-lactate dehydrogenase]] | [[Category: L-lactate dehydrogenase]] | ||
[[Category: Dempster, S | [[Category: Dempster, S]] | ||
[[Category: Dreveny, I | [[Category: Dreveny, I]] | ||
[[Category: Harper, S | [[Category: Harper, S]] | ||
[[Category: Moses, J E | [[Category: Moses, J E]] | ||
[[Category: Anaerobic respiration]] | [[Category: Anaerobic respiration]] | ||
[[Category: Glycolysis]] | [[Category: Glycolysis]] | ||
[[Category: Oxidoreductase]] | [[Category: Oxidoreductase]] | ||
Revision as of 06:14, 25 December 2014
Structural characterisation of the NADH binary complex of human lactate dehydrogenase M isozymeStructural characterisation of the NADH binary complex of human lactate dehydrogenase M isozyme
Structural highlights
Disease[LDHA_HUMAN] Defects in LDHA are the cause of glycogen storage disease type 11 (GSD11) [MIM:612933]. A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue.[1] Publication Abstract from PubMedLactate dehydrogenase A (LDH-A) is a key enzyme in anaerobic respiration that is predominantly found in skeletal muscle and catalyses the reversible conversion of pyruvate to lactate in the presence of NADH. LDH-A is overexpressed in many tumours and has therefore emerged as an attractive target for anticancer drug discovery. Crystal structures of human LDH-A in the presence of inhibitors have been described, but currently no structures of the apo or binary NADH-bound forms are available for any mammalian LDH-A. Here, the apo structure of human LDH-A was solved at a resolution of 2.1 A in space group P4122. The active-site loop adopts an open conformation and the packing and crystallization conditions suggest that the crystal form is suitable for soaking experiments. The soaking potential was assessed with the cofactor NADH, which yielded a ligand-bound crystal structure in the absence of any inhibitors. The structures show that NADH binding induces small conformational changes in the active-site loop and an adjacent helix. A comparison with other eukaryotic apo LDH structures reveals the conservation of intra-loop interactions. The structures provide novel insight into cofactor binding and provide the foundation for soaking experiments with fragments and inhibitors. Structural characterization of the apo form and NADH binary complex of human lactate dehydrogenase.,Dempster S, Harper S, Moses JE, Dreveny I Acta Crystallogr D Biol Crystallogr. 2014 May;70(Pt 5):1484-90. doi:, 10.1107/S1399004714005422. Epub 2014 Apr 30. PMID:24816116[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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