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| | <StructureSection load='2nn7' size='340' side='right'caption='[[2nn7]], [[Resolution|resolution]] 1.85Å' scene=''> | | <StructureSection load='2nn7' size='340' side='right'caption='[[2nn7]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2nn7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NN7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NN7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2nn7]] is a 2 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=2NN7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NN7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=M29:ETHYL+3-[4-(AMINOSULFONYL)PHENYL]PROPANOATE'>M29</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.85Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2nmx|2nmx]], [[2nn1|2nn1]], [[2nng|2nng]], [[2nno|2nno]], [[2nns|2nns]], [[2nnv|2nnv]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=M29:ETHYL+3-[4-(AMINOSULFONYL)PHENYL]PROPANOATE'>M29</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CA1 ([https://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'>[https://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2nn7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nn7 OCA], [https://pdbe.org/2nn7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nn7 RCSB], [https://www.ebi.ac.uk/pdbsum/2nn7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nn7 ProSAT]</span></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=2nn7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nn7 OCA], [https://pdbe.org/2nn7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nn7 RCSB], [https://www.ebi.ac.uk/pdbsum/2nn7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nn7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CAH1_HUMAN CAH1_HUMAN]] Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.<ref>PMID:10550681</ref>
| + | [https://www.uniprot.org/uniprot/CAH1_HUMAN CAH1_HUMAN] Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.<ref>PMID:10550681</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Carbonate dehydratase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Christianson, D W]] | + | [[Category: Christianson DW]] |
| - | [[Category: Jude, K M]] | + | [[Category: Jude KM]] |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Zinc metalloenzyme]]
| + | |
| Structural highlights
Function
CAH1_HUMAN Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Despite the similarity in the active site pockets of carbonic anhydrase (CA) isozymes I and II, the binding affinities of benzenesulfonamide inhibitors are invariably higher with CA II as compared to CA I. To explore the structural basis of this molecular recognition phenomenon, we have designed and synthesized simple benzenesulfonamide inhibitors substituted at the para position with positively charged, negatively charged, and neutral functional groups, and we have determined the affinities and X-ray crystal structures of their enzyme complexes. The para-substituents are designed to bind in the midsection of the 15 A deep active site cleft, where interactions with enzyme residues and solvent molecules are possible. We find that a para-substituted positively charged amino group is more poorly tolerated in the active site of CA I compared with CA II. In contrast, a para-substituted negatively charged carboxylate substituent is tolerated equally well in the active sites of both CA isozymes. Notably, enzyme-inhibitor affinity increases upon neutralization of inhibitor charged groups by amidation or esterification. These results inform the design of short molecular linkers connecting the benzenesulfonamide group and a para-substituted tail group in "two-prong" CA inhibitors: an optimal linker segment will be electronically neutral, yet capable of engaging in at least some hydrogen bond interactions with protein residues and/or solvent. Microcalorimetric data reveal that inhibitor binding to CA I is enthalpically less favorable and entropically more favorable than inhibitor binding to CA II. This contrasting behavior may arise in part from differences in active site desolvation and the conformational entropy of inhibitor binding to each isozyme active site.
Structural analysis of charge discrimination in the binding of inhibitors to human carbonic anhydrases I and II.,Srivastava DK, Jude KM, Banerjee AL, Haldar M, Manokaran S, Kooren J, Mallik S, Christianson DW J Am Chem Soc. 2007 May 2;129(17):5528-37. Epub 2007 Apr 4. PMID:17407288[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Briganti F, Mangani S, Scozzafava A, Vernaglione G, Supuran CT. Carbonic anhydrase catalyzes cyanamide hydration to urea: is it mimicking the physiological reaction? J Biol Inorg Chem. 1999 Oct;4(5):528-36. PMID:10550681
- ↑ Srivastava DK, Jude KM, Banerjee AL, Haldar M, Manokaran S, Kooren J, Mallik S, Christianson DW. Structural analysis of charge discrimination in the binding of inhibitors to human carbonic anhydrases I and II. J Am Chem Soc. 2007 May 2;129(17):5528-37. Epub 2007 Apr 4. PMID:17407288 doi:10.1021/ja068359w
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