4g0c: Difference between revisions
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==Neutron structure of acetazolamide-bound human carbonic anhydrase II reveal molecular details of drug binding.== | ==Neutron structure of acetazolamide-bound human carbonic anhydrase II reveal molecular details of drug binding.== | ||
<StructureSection load='4g0c' size='340' side='right' caption='[[4g0c]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='4g0c' size='340' side='right' caption='[[4g0c]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4g0c]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4g0c]] is a 1 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=4G0C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G0C FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AZM:5-ACETAMIDO-1,3,4-THIADIAZOLE-2-SULFONAMIDE'>AZM</scene>, <scene name='pdbligand=DOD:DEUTERATED+WATER'>DOD</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=AZM:5-ACETAMIDO-1,3,4-THIADIAZOLE-2-SULFONAMIDE'>AZM</scene>, <scene name='pdbligand=DOD:DEUTERATED+WATER'>DOD</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">CA2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CA2 ([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=4g0c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g0c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4g0c RCSB], [http://www.ebi.ac.uk/pdbsum/4g0c 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=4g0c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g0c OCA], [http://pdbe.org/4g0c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4g0c RCSB], [http://www.ebi.ac.uk/pdbsum/4g0c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4g0c ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4g0c" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Carbonate dehydratase]] | [[Category: Carbonate dehydratase]] | ||
[[Category: | [[Category: Human]] | ||
[[Category: Aggarwal, M]] | [[Category: Aggarwal, M]] | ||
[[Category: Fisher, S Z]] | [[Category: Fisher, S Z]] | ||
Revision as of 01:33, 6 August 2016
Neutron structure of acetazolamide-bound human carbonic anhydrase II reveal molecular details of drug binding.Neutron structure of acetazolamide-bound human carbonic anhydrase II reveal molecular details of drug binding.
Structural highlights
Disease[CAH2_HUMAN] Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM:259730]; also known as osteopetrosis with renal tubular acidosis, carbonic anhydrase II deficiency syndrome, Guibaud-Vainsel syndrome or marble brain disease. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Autosomal recessive osteopetrosis is usually associated with normal or elevated amount of non-functional osteoclasts. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with mental retardation.[1] [2] [3] [4] [5] Function[CAH2_HUMAN] Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye.[6] [7] Publication Abstract from PubMedCarbonic anhydrases (CAs) catalyze the hydration of CO(2) forming HCO(3)(-) and a proton, an important reaction for many physiological processes including respiration, fluid secretion, and pH regulation. As such, CA isoforms are prominent clinical targets for treating various diseases. The clinically used acetazolamide (AZM) is a sulfonamide that binds with high affinity to human CA isoform II (HCA II). There are several X-ray structures available of AZM bound to various CA isoforms, but these complexes do not show the charged state of AZM or the hydrogen atom positions of the protein and solvent. Neutron diffraction is a useful technique for directly observing H atoms and the mapping of H-bonding networks that can greatly contribute to rational drug design. To this end, the neutron structure of H/D exchanged HCA II crystals in complex with AZM was determined. The structure reveals the molecular details of AZM binding and the charged state of the bound drug. This represents the first determined neutron structure of a clinically used drug bound to its target. Neutron Diffraction of Acetazolamide-Bound Human Carbonic Anhydrase II Reveals Atomic Details of Drug Binding.,Fisher SZ, Aggarwal M, Kovalevsky AY, Silverman DN, McKenna R J Am Chem Soc. 2012 Sep 12;134(36):14726-9. Epub 2012 Sep 4. PMID:22928733[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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