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New page: left|200px<br /> <applet load="1cil" size="450" color="white" frame="true" align="right" spinBox="true" caption="1cil, resolution 1.6Å" /> '''THE POSITIONS OF HIS...
 
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[[Image:1cil.gif|left|200px]]<br />
<applet load="1cil" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1cil, resolution 1.6&Aring;" />
'''THE POSITIONS OF HIS-64 AND A BOUND WATER IN HUMAN CARBONIC ANHYDRASE II UPON BINDING THREE STRUCTURALLY RELATED INHIBITORS'''<br />


==Overview==
==THE POSITIONS OF HIS-64 AND A BOUND WATER IN HUMAN CARBONIC ANHYDRASE II UPON BINDING THREE STRUCTURALLY RELATED INHIBITORS==
The 3-dimensional structure of human carbonic anhydrase II (HCAII; EC, 4.2.1.1) complexed with 3 structurally related inhibitors, 1a, 1b, and 1c, has been determined by X-ray crystallographic methods. The 3 inhibitors, (1a = C8H12N2O4S3) vary only in the length of the substituent on the, 4-amino group: 1a, proton; 1b, methyl; and 1c, ethyl. The binding, constants (Ki's) for 1a, 1b, and 1c to HCAII are 1.52, 1.88, and 0.37 nM, respectively. These structures were solved to learn if any structural, cause could be found for the difference in binding. In the complex with, inhibitors 1a and 1b, electron density can be observed for His-64 and a, bound water molecule in the native positions. When inhibitor 1c is bound, the side chain attached to the 4-amino group is positioned so that His-64, can only occupy the alternate position and the bound water is absent., While a variety of factors contribute to the observed binding constants, the major reason 1c binds tighter to HCAII than does 1a or 1b appears to, be entropy: the increase in entropy when the bound water molecule is, released contributes to the increase in binding and overcomes the small, penalty for putting the His-64 side chain in a higher energy state.
<StructureSection load='1cil' size='340' side='right'caption='[[1cil]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1cil]] 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=1CIL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CIL 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]] 1.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ETS:(4S-TRANS)-4-(ETHYLAMINO)-5,6-DIHYDRO-6-METHYL-4H-THIENO(2,3-B)THIOPYRAN-2-SULFONAMIDE-7,7-DIOXIDE'>ETS</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=1cil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cil OCA], [https://pdbe.org/1cil PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cil RCSB], [https://www.ebi.ac.uk/pdbsum/1cil PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cil 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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ci/1cil_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1cil ConSurf].
<div style="clear:both"></div>


==Disease==
==See Also==
Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611492 611492]]
*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
 
== References ==
==About this Structure==
<references/>
1CIL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN and ETS as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1CIL OCA].
__TOC__
 
</StructureSection>
==Reference==
Positions of His-64 and a bound water in human carbonic anhydrase II upon binding three structurally related inhibitors., Smith GM, Alexander RS, Christianson DW, McKeever BM, Ponticello GS, Springer JP, Randall WC, Baldwin JJ, Habecker CN, Protein Sci. 1994 Jan;3(1):118-25. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8142888 8142888]
[[Category: Carbonate dehydratase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Alexander, R.S.]]
[[Category: Alexander RS]]
[[Category: Baldwin, J.J.]]
[[Category: Baldwin JJ]]
[[Category: Christianson, D.W.]]
[[Category: Christianson DW]]
[[Category: Habecker, C.N.]]
[[Category: Habecker CN]]
[[Category: Mckeever, B.M.]]
[[Category: Mckeever BM]]
[[Category: Ponticello, G.S.]]
[[Category: Ponticello GS]]
[[Category: Randall, W.C.]]
[[Category: Randall WC]]
[[Category: Smith, G.M.]]
[[Category: Smith GM]]
[[Category: Springer, J.P.]]
[[Category: Springer JP]]
[[Category: ETS]]
[[Category: ZN]]
[[Category: lyase(oxo-acid)]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:21:59 2007''

Latest revision as of 09:43, 7 February 2024

THE POSITIONS OF HIS-64 AND A BOUND WATER IN HUMAN CARBONIC ANHYDRASE II UPON BINDING THREE STRUCTURALLY RELATED INHIBITORSTHE POSITIONS OF HIS-64 AND A BOUND WATER IN HUMAN CARBONIC ANHYDRASE II UPON BINDING THREE STRUCTURALLY RELATED INHIBITORS

Structural highlights

1cil 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 1.6Å
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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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

1cil, resolution 1.60Å

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