1if7: Difference between revisions

Revision as of 08:27, 11 September 2015

Carbonic Anhydrase II Complexed With (R)-N-(3-Indol-1-yl-2-methyl-propyl)-4-sulfamoyl-benzamideCarbonic Anhydrase II Complexed With (R)-N-(3-Indol-1-yl-2-methyl-propyl)-4-sulfamoyl-benzamide

Structural highlights

1if7 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	1if8, 1if9
Activity:	Carbonate dehydratase, with EC number 4.2.1.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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]

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

Combinatorial small molecule growth algorithm was used to design inhibitors for human carbonic anhydrase II. Two enantiomeric candidate molecules were predicted to bind with high potency (with R isomer binding stronger than S), but in two distinct conformations. The experiments verified that computational predictions concerning the binding affinities and the binding modes were correct for both isomers. The designed R isomer is the best-known inhibitor (K(d) approximately 30 pM) of human carbonic anhydrase II.

Combinatorial computational method gives new picomolar ligands for a known enzyme.,Grzybowski BA, Ishchenko AV, Kim CY, Topalov G, Chapman R, Christianson DW, Whitesides GM, Shakhnovich EI Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1270-3. Epub 2002 Jan 29. PMID:11818565^[8]

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

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ Grzybowski BA, Ishchenko AV, Kim CY, Topalov G, Chapman R, Christianson DW, Whitesides GM, Shakhnovich EI. Combinatorial computational method gives new picomolar ligands for a known enzyme. Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1270-3. Epub 2002 Jan 29. PMID:11818565 doi:10.1073/pnas.032673399

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OCA

[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] Grzybowski BA, Ishchenko AV, Kim CY, Topalov G, Chapman R, Christianson DW, Whitesides GM, Shakhnovich EI. Combinatorial computational method gives new picomolar ligands for a known enzyme. Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1270-3. Epub 2002 Jan 29. PMID:11818565 doi:10.1073/pnas.032673399

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[3]

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@@ Line 2: / Line 2: @@
 <StructureSection load='1if7' size='340' side='right' caption='[[1if7]], [[Resolution|resolution]] 1.98&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1if7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IF7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1IF7 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1if7]] 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=1IF7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1IF7 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=SBR:(R)-N-(3-INDOL-1-YL-2-METHYL-PROPYL)-4-SULFAMOYL-BENZAMIDE'>SBR</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">[[1if8|1if8]], [[1if9|1if9]]</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=1if7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1if7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1if7 RCSB], [http://www.ebi.ac.uk/pdbsum/1if7 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=1if7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1if7 OCA], [http://pdbe.org/1if7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1if7 RCSB], [http://www.ebi.ac.uk/pdbsum/1if7 PDBsum]</span></td></tr>
 </table>
 == Disease ==
@@ Line 30: / Line 30: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1if7" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 38: / Line 39: @@
 </StructureSection>
 [[Category: Carbonate dehydratase]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Chapman, R]]
 [[Category: Christianson, D W]]

1if7: Difference between revisions

Revision as of 08:27, 11 September 2015

Carbonic Anhydrase II Complexed With (R)-N-(3-Indol-1-yl-2-methyl-propyl)-4-sulfamoyl-benzamideCarbonic Anhydrase II Complexed With (R)-N-(3-Indol-1-yl-2-methyl-propyl)-4-sulfamoyl-benzamide

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

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Navigation menu

1if7: Difference between revisions

Revision as of 08:27, 11 September 2015

Carbonic Anhydrase II Complexed With (R)-N-(3-Indol-1-yl-2-methyl-propyl)-4-sulfamoyl-benzamideCarbonic Anhydrase II Complexed With (R)-N-(3-Indol-1-yl-2-methyl-propyl)-4-sulfamoyl-benzamide

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Search