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3sgz

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High resolution crystal structure of rat long chain hydroxy acid oxidase in complex with the inhibitor 4-carboxy-5-[(4-chiorophenyl)sulfanyl]-1, 2, 3-thiadiazole.

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 ==High resolution crystal structure of rat long chain hydroxy acid oxidase in complex with the inhibitor 4-carboxy-5-[(4-chiorophenyl)sulfanyl]-1, 2, 3-thiadiazole.==
-<StructureSection load='3sgz' size='340' side='right' caption='[[3sgz]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
+<StructureSection load='3sgz' size='340' side='right'caption='[[3sgz]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3sgz]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SGZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SGZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3sgz]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SGZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SGZ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=HO6:5-[(4-METHYLPHENYL)SULFANYL]-1,2,3-THIADIAZOLE-4-CARBOXYLIC+ACID'>HO6</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]] 1.35&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1tb3|1tb3]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=HO6:5-[(4-METHYLPHENYL)SULFANYL]-1,2,3-THIADIAZOLE-4-CARBOXYLIC+ACID'>HO6</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Hao2, Hao3, Haox2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</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=3sgz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sgz OCA], [https://pdbe.org/3sgz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sgz RCSB], [https://www.ebi.ac.uk/pdbsum/3sgz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sgz ProSAT]</span></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/(S)-2-hydroxy-acid_oxidase (S)-2-hydroxy-acid oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.3.15 1.1.3.15] </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=3sgz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sgz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sgz RCSB], [http://www.ebi.ac.uk/pdbsum/3sgz PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/HAOX2_RAT HAOX2_RAT]] Catalyzes the oxidation of L-alpha-hydroxy acids as well as, more slowly, that of L-alpha-amino acids.
+[https://www.uniprot.org/uniprot/HAOX2_RAT HAOX2_RAT] Catalyzes the oxidation of L-alpha-hydroxy acids as well as, more slowly, that of L-alpha-amino acids.
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-Long chain hydroxy acid oxidase (LCHAO) is responsible for the formation of methylguanidine, a toxic compound with elevated serum levels in patients with chronic renal failure. Its isozyme glycolate oxidase (GOX), has a role in the formation of oxalate, which can lead to pathological deposits of calcium oxalate, in particular in the disease primary hyperoxaluria. Inhibitors of these two enzymes may have therapeutic value. These enzymes are the only human members of the family of FMN-dependent l-2-hydroxy acid-oxidizing enzymes, with yeast flavocytochrome b(2) (Fcb2) among its well studied members. We screened a chemical library for inhibitors, using in parallel rat LCHAO, human GOX and the Fcb2 flavodehydrogenase domain (FDH). Among the hits was an inhibitor, CCPST, with an IC(50) in the micromolar range for all three enzymes. We report here the crystal structure of a complex between this compound and LCHAO at 1.3 A resolution. In comparison with a lower resolution structure of this enzyme, binding of the inhibitor induces a conformational change in part of the TIM barrel loop 4, as well as protonation of the active site histidine. The CCPST interactions are compared with those it forms with human GOX and those formed by two other inhibitors with human GOX and spinach GOX. These compounds differ from CCPST in having the sulfur replaced with a nitrogen in the five-membered ring as well as different hydrophobic substituents. The possible reason for the approximately 100-fold difference in affinity between these two series of inhibitors is discussed. The present results indicate that specificity is an issue in the quest for therapeutic inhibitors of either LCHAO or GOX, but they may give leads for this quest.
-High resolution crystal structure of rat long chain hydroxy acid oxidase in complex with the inhibitor 4-carboxy-5-[(4-chlorophenyl)sulfanyl]-1, 2, 3-thiadiazole. Implications for inhibitor specificity and drug design.,Chen ZW, Vignaud C, Jaafar A, Levy B, Gueritte F, Guenard D, Lederer F, Mathews FS Biochimie. 2012 Feb 9. PMID:22342614<ref>PMID:22342614</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
 ==See Also==
-*[[Glycolate oxidase|Glycolate oxidase]]
+*[[Glycolate oxidase 3D structures|Glycolate oxidase 3D structures]]
-== References ==
-<references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Rattus norvegicus]]
-[[Category: Chen, Z]]
+[[Category: Chen Z]]
-[[Category: Guenard, D]]
+[[Category: Guenard D]]
-[[Category: Gueritte, F]]
+[[Category: Gueritte F]]
-[[Category: Jaafar, A]]
+[[Category: Jaafar A]]
-[[Category: Lederer, F]]
+[[Category: Lederer F]]
-[[Category: Mathews, F S]]
+[[Category: Mathews FS]]
-[[Category: Vignaud, C]]
+[[Category: Vignaud C]]
-[[Category: Flavoprotein]]
-[[Category: Homology]]
-[[Category: Inhibitor]]
-[[Category: Long chain hydroxy acid oxidase]]
-[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

3sgz

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High resolution crystal structure of rat long chain hydroxy acid oxidase in complex with the inhibitor 4-carboxy-5-[(4-chiorophenyl)sulfanyl]-1, 2, 3-thiadiazole.

Structural highlights

Function

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