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==CRYSTAL STRUCTURE OF HUMAN CA II IN COMPLEX WITH 2-MERCAPTOBENZOXAZOLE==
==CRYSTAL STRUCTURE OF HUMAN CA II IN COMPLEX WITH 2-MERCAPTOBENZOXAZOLE==
<StructureSection load='6yqu' size='340' side='right'caption='[[6yqu]]' scene=''>
<StructureSection load='6yqu' size='340' side='right'caption='[[6yqu]], [[Resolution|resolution]] 1.48&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YQU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YQU FirstGlance]. <br>
<table><tr><td colspan='2'>[[6yqu]] 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=6YQU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YQU FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6yqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yqu OCA], [http://pdbe.org/6yqu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6yqu RCSB], [http://www.ebi.ac.uk/pdbsum/6yqu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6yqu ProSAT]</span></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]] 1.478&#8491;</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=P92:3~{H}-1,3-benzoxazole-2-thione'>P92</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=6yqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yqu OCA], [https://pdbe.org/6yqu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yqu RCSB], [https://www.ebi.ac.uk/pdbsum/6yqu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yqu ProSAT]</span></td></tr>
</table>
</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 ==
2-Mercaptobenzoxazole is a widely used organic scaffold in medicinal chemistry. By means of kinetic and structural studies, we demonstrate that this molecule can effectively be used to inhibit hCAs showing a peculiar binding mode. The results reported here can pave the way for the development of selective CA inhibitors.
2-Mercaptobenzoxazoles: a class of carbonic anhydrase inhibitors with a novel binding mode to the enzyme active site.,Bozdag M, Supuran CT, Esposito D, Angeli A, Carta F, Monti SM, De Simone G, Alterio V Chem Commun (Camb). 2020 Jun 23. doi: 10.1039/d0cc02857f. PMID:32573627<ref>PMID:32573627</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6yqu" style="background-color:#fffaf0;"></div>
==See Also==
*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Alterio V]]
[[Category: Alterio V]]
[[Category: De Simone G]]
[[Category: De Simone G]]
[[Category: Esposito D]]
[[Category: Esposito D]]

Latest revision as of 16:33, 24 January 2024

CRYSTAL STRUCTURE OF HUMAN CA II IN COMPLEX WITH 2-MERCAPTOBENZOXAZOLECRYSTAL STRUCTURE OF HUMAN CA II IN COMPLEX WITH 2-MERCAPTOBENZOXAZOLE

Structural highlights

6yqu is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.478Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 PubMed

2-Mercaptobenzoxazole is a widely used organic scaffold in medicinal chemistry. By means of kinetic and structural studies, we demonstrate that this molecule can effectively be used to inhibit hCAs showing a peculiar binding mode. The results reported here can pave the way for the development of selective CA inhibitors.

2-Mercaptobenzoxazoles: a class of carbonic anhydrase inhibitors with a novel binding mode to the enzyme active site.,Bozdag M, Supuran CT, Esposito D, Angeli A, Carta F, Monti SM, De Simone G, Alterio V Chem Commun (Camb). 2020 Jun 23. doi: 10.1039/d0cc02857f. PMID:32573627[8]

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

See Also

References

  1. ↑ Venta PJ, Welty RJ, Johnson TM, Sly WS, Tashian RE. Carbonic anhydrase II deficiency syndrome in a Belgian family is caused by a point mutation at an invariant histidine residue (107 His----Tyr): complete structure of the normal human CA II gene. Am J Hum Genet. 1991 Nov;49(5):1082-90. PMID:1928091
  2. ↑ Roth DE, Venta PJ, Tashian RE, Sly WS. Molecular basis of human carbonic anhydrase II deficiency. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1804-8. PMID:1542674
  3. ↑ Soda H, Yukizane S, Yoshida I, Koga Y, Aramaki S, Kato H. A point mutation in exon 3 (His 107-->Tyr) in two unrelated Japanese patients with carbonic anhydrase II deficiency with central nervous system involvement. Hum Genet. 1996 Apr;97(4):435-7. PMID:8834238
  4. ↑ Hu PY, Lim EJ, Ciccolella J, Strisciuglio P, Sly WS. Seven novel mutations in carbonic anhydrase II deficiency syndrome identified by SSCP and direct sequencing analysis. Hum Mutat. 1997;9(5):383-7. PMID:9143915 doi:<383::AID-HUMU1>3.0.CO;2-5 10.1002/(SICI)1098-1004(1997)9:5<383::AID-HUMU1>3.0.CO;2-5
  5. ↑ Shah GN, Bonapace G, Hu PY, Strisciuglio P, Sly WS. Carbonic anhydrase II deficiency syndrome (osteopetrosis with renal tubular acidosis and brain calcification): novel mutations in CA2 identified by direct sequencing expand the opportunity for genotype-phenotype correlation. Hum Mutat. 2004 Sep;24(3):272. PMID:15300855 doi:10.1002/humu.9266
  6. ↑ 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
  7. ↑ Kim CY, Whittington DA, Chang JS, Liao J, May JA, Christianson DW. Structural aspects of isozyme selectivity in the binding of inhibitors to carbonic anhydrases II and IV. J Med Chem. 2002 Feb 14;45(4):888-93. PMID:11831900
  8. ↑ Bozdag M, Supuran CT, Esposito D, Angeli A, Carta F, Monti SM, De Simone G, Alterio V. 2-Mercaptobenzoxazoles: a class of carbonic anhydrase inhibitors with a novel binding mode to the enzyme active site. Chem Commun (Camb). 2020 Jul 23;56(59):8297-8300. PMID:32573627 doi:10.1039/d0cc02857f

6yqu, resolution 1.48Å

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