6hr3: Difference between revisions
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The | ==Human Carbonic Anhydrase II in complex with 4-Propylbenzenesulfonamide== | ||
<StructureSection load='6hr3' size='340' side='right'caption='[[6hr3]], [[Resolution|resolution]] 1.02Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6hr3]] is a 1 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=6HR3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HR3 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.02Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4JE:4-PROPYLBENZENESULFONAMIDE'>4JE</scene>, <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=MBO:MERCURIBENZOIC+ACID'>MBO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6hr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hr3 OCA], [https://pdbe.org/6hr3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hr3 RCSB], [https://www.ebi.ac.uk/pdbsum/6hr3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hr3 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/CAH2_HUMAN CAH2_HUMAN] Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM:[https://omim.org/entry/259730 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.<ref>PMID:1928091</ref> <ref>PMID:1542674</ref> <ref>PMID:8834238</ref> <ref>PMID:9143915</ref> <ref>PMID:15300855</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CAH2_HUMAN 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.<ref>PMID:10550681</ref> <ref>PMID:11831900</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Thermodynamics and kinetics of protein-ligand binding are both important aspects for the design of novel drug molecules. Presently, thermodynamic data are collected with isothermal titration calorimetry, while kinetic data are mostly derived from surface plasmon resonance. The new method of kinITC provides both thermodynamic and kinetic data from calorimetric titration measurements. The present study demonstrates the convenient collection of calorimetric data suitable for both thermodynamic and kinetic analysis for two series of congeneric ligands of human carbonic anhydrase II and correlates these findings with structural data obtained by macromolecular crystallography to shed light on the importance of shape complementarity for thermodynamics and kinetics governing a protein-ligand binding event. The study shows how minute chemical alterations change preferred ligand conformation and can be used to manipulate thermodynamic and kinetic signatures of binding. They give rise to the observation that analogous n-alkyl and n-alkyloxy derivatives of identical chain length swap their binding kinetic properties at unchanged binding affinity. | |||
Conformational Changes in Alkyl Chains Determine the Thermodynamic and Kinetic Binding Profiles of Carbonic Anhydrase Inhibitors.,Glockner S, Ngo K, Sager CP, Hufner-Wulsdorf T, Heine A, Klebe G ACS Chem Biol. 2020 Mar 20;15(3):675-685. doi: 10.1021/acschembio.9b00895. Epub, 2020 Feb 19. PMID:32027480<ref>PMID:32027480</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Gloeckner | <div class="pdbe-citations 6hr3" style="background-color:#fffaf0;"></div> | ||
[[Category: Heine | |||
[[Category: Klebe | ==See Also== | ||
*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Gloeckner S]] | |||
[[Category: Heine A]] | |||
[[Category: Klebe G]] | |||
Latest revision as of 14:37, 24 January 2024
Human Carbonic Anhydrase II in complex with 4-PropylbenzenesulfonamideHuman Carbonic Anhydrase II in complex with 4-Propylbenzenesulfonamide
Structural highlights
DiseaseCAH2_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] FunctionCAH2_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 PubMedThermodynamics and kinetics of protein-ligand binding are both important aspects for the design of novel drug molecules. Presently, thermodynamic data are collected with isothermal titration calorimetry, while kinetic data are mostly derived from surface plasmon resonance. The new method of kinITC provides both thermodynamic and kinetic data from calorimetric titration measurements. The present study demonstrates the convenient collection of calorimetric data suitable for both thermodynamic and kinetic analysis for two series of congeneric ligands of human carbonic anhydrase II and correlates these findings with structural data obtained by macromolecular crystallography to shed light on the importance of shape complementarity for thermodynamics and kinetics governing a protein-ligand binding event. The study shows how minute chemical alterations change preferred ligand conformation and can be used to manipulate thermodynamic and kinetic signatures of binding. They give rise to the observation that analogous n-alkyl and n-alkyloxy derivatives of identical chain length swap their binding kinetic properties at unchanged binding affinity. Conformational Changes in Alkyl Chains Determine the Thermodynamic and Kinetic Binding Profiles of Carbonic Anhydrase Inhibitors.,Glockner S, Ngo K, Sager CP, Hufner-Wulsdorf T, Heine A, Klebe G ACS Chem Biol. 2020 Mar 20;15(3):675-685. doi: 10.1021/acschembio.9b00895. Epub, 2020 Feb 19. PMID:32027480[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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