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4r68

From Proteopedia

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Lactate Dehydrogenase in complex with inhibitor compound 31

Structural highlights

4r68 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.112Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Function

LDHA_HUMAN

Publication Abstract from PubMed

Optimization of 5-(2,6-dichlorophenyl)-3-hydroxy-2-mercaptocyclohex-2-enone using structure-based design strategies resulted in inhibitors with considerable improvement in biochemical potency against human lactate dehydrogenase A (LDHA). These potent inhibitors were typically selective for LDHA over LDHB isoform (4-10 fold) and other structurally related malate dehydrogenases, MDH1 and MDH2 (>500 fold). An X-ray crystal structure of enzymatically most potent molecule bound to LDHA revealed two additional interactions associated with enhanced biochemical potency.

Optimization of 5-(2,6-dichlorophenyl)-3-hydroxy-2-mercaptocyclohex-2-enones as potent inhibitors of human lactate dehydrogenase.,Labadie S, Dragovich PS, Chen J, Fauber BP, Boggs J, Corson LB, Ding CZ, Eigenbrot C, Ge H, Ho Q, Lai KW, Ma S, Malek S, Peterson D, Purkey HE, Robarge K, Salphati L, Sideris S, Ultsch M, VanderPorten E, Wei B, Xu Q, Yen I, Yue Q, Zhang H, Zhang X, Zhou A Bioorg Med Chem Lett. 2014 Nov 10;25(1):75-82. doi: 10.1016/j.bmcl.2014.11.008. PMID:25466195^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Maekawa M, Sudo K, Kanno T, Li SS. Molecular characterization of genetic mutation in human lactate dehydrogenase-A (M) deficiency. Biochem Biophys Res Commun. 1990 Apr 30;168(2):677-82. PMID:2334430
↑ Labadie S, Dragovich PS, Chen J, Fauber BP, Boggs J, Corson LB, Ding CZ, Eigenbrot C, Ge H, Ho Q, Lai KW, Ma S, Malek S, Peterson D, Purkey HE, Robarge K, Salphati L, Sideris S, Ultsch M, VanderPorten E, Wei B, Xu Q, Yen I, Yue Q, Zhang H, Zhang X, Zhou A. Optimization of 5-(2,6-dichlorophenyl)-3-hydroxy-2-mercaptocyclohex-2-enones as potent inhibitors of human lactate dehydrogenase. Bioorg Med Chem Lett. 2014 Nov 10;25(1):75-82. doi: 10.1016/j.bmcl.2014.11.008. PMID:25466195 doi:http://dx.doi.org/10.1016/j.bmcl.2014.11.008

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4r68"

Categories: Homo sapiens | Large Structures | Eigenbrot C | Ultsch M

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4r68]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R68 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R68 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=W31:(1S)-1-PHENYLETHYL+(4-CHLORO-3-{[(4S)-4-(2,6-DICHLOROPHENYL)-2-HYDROXY-6-OXOCYCLOHEX-1-EN-1-YL]SULFANYL}PHENYL)ACETATE'>W31</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.112&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=W31:(1S)-1-PHENYLETHYL+(4-CHLORO-3-{[(4S)-4-(2,6-DICHLOROPHENYL)-2-HYDROXY-6-OXOCYCLOHEX-1-EN-1-YL]SULFANYL}PHENYL)ACETATE'>W31</scene></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=4r68 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r68 OCA], [https://pdbe.org/4r68 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r68 RCSB], [https://www.ebi.ac.uk/pdbsum/4r68 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r68 ProSAT]</span></td></tr>
 </table>

4r68

From Proteopedia

Current revision

Lactate Dehydrogenase in complex with inhibitor compound 31

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

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