4qj0

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Revision as of 17:14, 18 January 2017

Crystal structure of catalytic domain of human carbonic anhydrase isozyme XII with inhibitor

Structural highlights

4qj0 is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	4qiy, 4qiz, 4qjm, 4qjo, 4qjp, 4qjw, 4qjx, 4qtl
Activity:	Carbonate dehydratase, with EC number 4.2.1.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CAH12_HUMAN] Defects in CA12 are the cause of hyperchlorhidrosis isolated (HCHLH) [MIM:143860]. HCHLH is a disorder characterized by excessive sweating and increased sweat chloride levels. Affected individuals suffer from episodes of hyponatremic dehydration and report increased amounts of visible salt precipitates in sweat.^[1]

Function

[CAH12_HUMAN] Reversible hydration of carbon dioxide.

Publication Abstract from PubMed

Substituted tri- and tetrafluorobenzenesulfonamides were designed, synthesized, and evaluated as high-affinity and isoform-selective carbonic anhydrase (CA) inhibitors. Their binding affinities for recombinant human CA I, II, VA, VI, VII, XII, and XIII catalytic domains were determined by fluorescent thermal shift assay, isothermal titration calorimetry, and a stopped-flow CO2 hydration assay. Variation of the substituents at the 2-, 3-, and 4-positions yielded compounds with a broad range of binding affinities and isoform selectivities. Several 2,4-substituted-3,5,6-trifluorobenzenesulfonamides were effective CA XIII inhibitors with high selectivity over off-target CA I and CA II. 3,4-Disubstituted-2,5,6-trifluorobenzenesulfonamides bound CAs with higher affinity than 2,4-disubstituted-3,5,6-trifluorobenzenesulfonamides. Many such fluorinated benzenesulfonamides were found to be nanomolar inhibitors of CA II, CA VII, tumor-associated CA IX and CA XII, and CA XIII. X-ray crystal structures of inhibitors bound in the active sites of several CA isoforms provide structure-activity relationship information for inhibitor binding affinities and selectivity.

Functionalization of Fluorinated Benzenesulfonamides and Their Inhibitory Properties toward Carbonic Anhydrases.,Dudutiene V, Zubriene A, Smirnov A, Timm DD, Smirnoviene J, Kazokaite J, Michailoviene V, Zaksauskas A, Manakova E, Grazulis S, Matulis D ChemMedChem. 2015 Apr;10(4):662-87. doi: 10.1002/cmdc.201402490. Epub 2015 Mar, 10. PMID:25758852^[2]

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

References

↑ Feldshtein M, Elkrinawi S, Yerushalmi B, Marcus B, Vullo D, Romi H, Ofir R, Landau D, Sivan S, Supuran CT, Birk OS. Hyperchlorhidrosis caused by homozygous mutation in CA12, encoding carbonic anhydrase XII. Am J Hum Genet. 2010 Nov 12;87(5):713-20. doi: 10.1016/j.ajhg.2010.10.008. Epub, 2010 Oct 28. PMID:21035102 doi:10.1016/j.ajhg.2010.10.008
↑ Dudutiene V, Zubriene A, Smirnov A, Timm DD, Smirnoviene J, Kazokaite J, Michailoviene V, Zaksauskas A, Manakova E, Grazulis S, Matulis D. Functionalization of Fluorinated Benzenesulfonamides and Their Inhibitory Properties toward Carbonic Anhydrases. ChemMedChem. 2015 Apr;10(4):662-87. doi: 10.1002/cmdc.201402490. Epub 2015 Mar, 10. PMID:25758852 doi:http://dx.doi.org/10.1002/cmdc.201402490

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4qj0"

@@ Line 1: / Line 1: @@
 ==Crystal structure of catalytic domain of human carbonic anhydrase isozyme XII with inhibitor==
 <StructureSection load='4qj0' size='340' side='right' caption='[[4qj0]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4qiy|4qiy]], [[4qiz|4qiz]], [[4qjm|4qjm]], [[4qjo|4qjo]], [[4qjp|4qjp]], [[4qjw|4qjw]], [[4qjx|4qjx]], [[4qtl|4qtl]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] </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=4qj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qj0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qj0 RCSB], [http://www.ebi.ac.uk/pdbsum/4qj0 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=4qj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qj0 OCA], [http://pdbe.org/4qj0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qj0 RCSB], [http://www.ebi.ac.uk/pdbsum/4qj0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qj0 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 21: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4qj0" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4qj0

From Proteopedia

Revision as of 17:14, 18 January 2017

Crystal structure of catalytic domain of human carbonic anhydrase isozyme XII with inhibitor

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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