5msb: Difference between revisions
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<StructureSection load='5msb' size='340' side='right' caption='[[5msb]], [[Resolution|resolution]] 1.30Å' scene=''> | <StructureSection load='5msb' size='340' side='right' caption='[[5msb]], [[Resolution|resolution]] 1.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5msb]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MSB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MSB FirstGlance]. <br> | <table><tr><td colspan='2'>[[5msb]] is a 4 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=5MSB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MSB FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=V13:2,3,5,6-TETRAFLUORO-4-[(2-HYDROXYETHYL)SULFONYL]BENZENESULFONAMIDE'>V13</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=V13:2,3,5,6-TETRAFLUORO-4-[(2-HYDROXYETHYL)SULFONYL]BENZENESULFONAMIDE'>V13</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5llc|5llc]], [[5lle|5lle]], [[5llg|5llg]], [[5llh|5llh]], [[5lln|5lln]], [[5llo|5llo]], [[5llp|5llp]], [[5msa|5msa]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5llc|5llc]], [[5lle|5lle]], [[5llg|5llg]], [[5llh|5llh]], [[5lln|5lln]], [[5llo|5llo]], [[5llp|5llp]], [[5msa|5msa]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CA12 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='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=5msb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5msb OCA], [http://pdbe.org/5msb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5msb RCSB], [http://www.ebi.ac.uk/pdbsum/5msb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5msb ProSAT]</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=5msb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5msb OCA], [http://pdbe.org/5msb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5msb RCSB], [http://www.ebi.ac.uk/pdbsum/5msb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5msb ProSAT]</span></td></tr> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/CAH12_HUMAN CAH12_HUMAN]] Reversible hydration of carbon dioxide. | [[http://www.uniprot.org/uniprot/CAH12_HUMAN CAH12_HUMAN]] Reversible hydration of carbon dioxide. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The structure-thermodynamics correlation analysis was performed for a series of fluorine- and chlorine-substituted benzenesulfonamide inhibitors binding to several human carbonic anhydrase (CA) isoforms. The total of 24 crystal structures of 16 inhibitors bound to isoforms CA I, CA II, CA XII, and CA XIII provided the structural information of selective recognition between a compound and CA isoform. The binding thermodynamics of all structures was determined by the analysis of binding-linked protonation events, yielding the intrinsic parameters, i.e., the enthalpy, entropy, and Gibbs energy of binding. Inhibitor binding was compared within structurally similar pairs that differ by para- or meta-substituents enabling to obtain the contributing energies of ligand fragments. The pairs were divided into two groups. First, similar binders-the pairs that keep the same orientation of the benzene ring exhibited classical hydrophobic effect, a less exothermic enthalpy and a more favorable entropy upon addition of the hydrophobic fragments. Second, dissimilar binders-the pairs of binders that demonstrated altered positions of the benzene rings exhibited the non-classical hydrophobic effect, a more favorable enthalpy and variable entropy contribution. A deeper understanding of the energies contributing to the protein-ligand recognition should lead toward the eventual goal of rational drug design where chemical structures of ligands could be designed based on the target protein structure. | |||
Crystal structure correlations with the intrinsic thermodynamics of human carbonic anhydrase inhibitor binding.,Smirnov A, Zubriene A, Manakova E, Grazulis S, Matulis D PeerJ. 2018 Feb 26;6:e4412. doi: 10.7717/peerj.4412. eCollection 2018. PMID:29503769<ref>PMID:29503769</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5msb" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Carbonic anhydrase|Carbonic anhydrase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Carbonate dehydratase]] | [[Category: Carbonate dehydratase]] | ||
[[Category: Human]] | |||
[[Category: Grazulis, S]] | [[Category: Grazulis, S]] | ||
[[Category: Manakova, E]] | [[Category: Manakova, E]] | ||
Revision as of 08:46, 16 May 2018
Crystal structure of human carbonic anhydrase isozyme XII with 2,3,5,6-tetrafluoro-4[(2-hydroxyethyl)sulfonyl]benzenesulfonamideCrystal structure of human carbonic anhydrase isozyme XII with 2,3,5,6-tetrafluoro-4[(2-hydroxyethyl)sulfonyl]benzenesulfonamide
Structural highlights
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 PubMedThe structure-thermodynamics correlation analysis was performed for a series of fluorine- and chlorine-substituted benzenesulfonamide inhibitors binding to several human carbonic anhydrase (CA) isoforms. The total of 24 crystal structures of 16 inhibitors bound to isoforms CA I, CA II, CA XII, and CA XIII provided the structural information of selective recognition between a compound and CA isoform. The binding thermodynamics of all structures was determined by the analysis of binding-linked protonation events, yielding the intrinsic parameters, i.e., the enthalpy, entropy, and Gibbs energy of binding. Inhibitor binding was compared within structurally similar pairs that differ by para- or meta-substituents enabling to obtain the contributing energies of ligand fragments. The pairs were divided into two groups. First, similar binders-the pairs that keep the same orientation of the benzene ring exhibited classical hydrophobic effect, a less exothermic enthalpy and a more favorable entropy upon addition of the hydrophobic fragments. Second, dissimilar binders-the pairs of binders that demonstrated altered positions of the benzene rings exhibited the non-classical hydrophobic effect, a more favorable enthalpy and variable entropy contribution. A deeper understanding of the energies contributing to the protein-ligand recognition should lead toward the eventual goal of rational drug design where chemical structures of ligands could be designed based on the target protein structure. Crystal structure correlations with the intrinsic thermodynamics of human carbonic anhydrase inhibitor binding.,Smirnov A, Zubriene A, Manakova E, Grazulis S, Matulis D PeerJ. 2018 Feb 26;6:e4412. doi: 10.7717/peerj.4412. eCollection 2018. PMID:29503769[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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