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4rn4

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Revision as of 09:37, 1 May 2019

Human Carbonic anhydrases II in complex with a acetazolamide derivative comprising one hydrophobic and one hydrophilic tail moiety

Structural highlights

4rn4 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:	, , ,
Gene:	CA2 (HUMAN)
Activity:	Carbonate dehydratase, with EC number 4.2.1.1
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

We present a new approach to carbonic anhydrase II (CA II) inhibitor design that enables close interrogation of the regions of the CA active site where there is the greatest variability in amino acid residues among the different CA isozymes. By appending dual tail groups onto the par excellence CA inhibitor acetazolamide, compounds that may interact with the distinct hydrophobic and hydrophilic halves of the CA II active site were prepared. The dual-tail combinations selected included (i) two hydrophobic moieties, (ii) two hydrophilic moieties, and (iii) one hydrophobic and one hydrophilic moiety. The CA enzyme inhibition profile as well as the protein X-ray crystal structure of compound 3, comprising one hydrophobic and one hydrophilic tail moiety, in complex with CA II is described. This novel dual-tail approach has provided an enhanced opportunity to more fully exploit interactions with the CA active site by enabling these molecules to interact with the distinct halves of the active site. In addition to the dual-tail compounds, a corresponding set of single-tail derivatives was synthesized, enabling a comparative analysis of the single-tail versus dual-tail compound CA inhibition profile.

Carbonic Anhydrase Inhibitors with Dual-Tail Moieties To Match the Hydrophobic and Hydrophilic Halves of the Carbonic Anhydrase Active Site.,Tanpure RP, Ren B, Peat TS, Bornaghi LF, Vullo D, Supuran CT, Poulsen SA J Med Chem. 2015 Jan 27. PMID:25581127^[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
↑ Tanpure RP, Ren B, Peat TS, Bornaghi LF, Vullo D, Supuran CT, Poulsen SA. Carbonic Anhydrase Inhibitors with Dual-Tail Moieties To Match the Hydrophobic and Hydrophilic Halves of the Carbonic Anhydrase Active Site. J Med Chem. 2015 Jan 27. PMID:25581127 doi:http://dx.doi.org/10.1021/jm501798g

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4rn4"

@@ Line 1: / Line 1: @@
 ==Human Carbonic anhydrases II in complex with a acetazolamide derivative comprising one hydrophobic and one hydrophilic tail moiety==
-<StructureSection load='4rn4' size='340' side='right' caption='[[4rn4]], [[Resolution|resolution]] 1.53&Aring;' scene=''>
+<StructureSection load='4rn4' size='340' side='right'caption='[[4rn4]], [[Resolution|resolution]] 1.53&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4rn4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RN4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RN4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4rn4]] 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=4RN4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RN4 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3T7:2-({[1-(BETA-D-GLUCOPYRANOSYL)-1H-1,2,3-TRIAZOL-4-YL]METHYL}[(1-PHENYL-1H-1,2,3-TRIAZOL-4-YL)METHYL]AMINO)-5-SULFAMOYL-1,3,4-THIADIAZOLE'>3T7</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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 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='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=4rn4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rn4 OCA], [http://pdbe.org/4rn4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rn4 RCSB], [http://www.ebi.ac.uk/pdbsum/4rn4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rn4 ProSAT]</span></td></tr>
@@ Line 23: / Line 24: @@
 ==See Also==
-*[[Carbonic anhydrase|Carbonic anhydrase]]
+*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
 == References ==
 <references/>
@@ Line 29: / Line 30: @@
 </StructureSection>
 [[Category: Carbonate dehydratase]]
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Bornaghi, L F]]
 [[Category: Peat, T S]]

4rn4

From Proteopedia

Revision as of 09:37, 1 May 2019

Human Carbonic anhydrases II in complex with a acetazolamide derivative comprising one hydrophobic and one hydrophilic tail moiety

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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