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1cal

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Revision as of 06:47, 10 October 2019

STRUCTURAL ANALYSIS OF THE ZINC HYDROXIDE-THR 199-GLU 106 HYDROGEN BONDING NETWORK IN HUMAN CARBONIC ANHYDRASE II

Structural highlights

1cal 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:
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]

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

The significance of the zinc hydroxide-Thr-199-Glu-106 hydrogen-bond network in the active site of human carbonic anhydrase II has been examined by X-ray crystallographic analyses of site-specific mutants. Mutants with Ala-199 and Ala-106 or Gln-106 have low catalytic activities, while a mutant with Asp-106 has almost full CO2 hydration activity. The structures of these four mutants, as well as that of the bicarbonate complex of the mutant with Ala-199, have been determined at 1.7 to 2.2 A resolution. Removal of the gamma atoms of residue 199 leads to a distorted tetrahedral geometry at the zinc ion, and a catalytically important zinc-bound water molecule has moved towards Glu-106. In the bicarbonate complex of the mutant with Ala-199 one oxygen atom from bicarbonate binds to zinc without displacing this water molecule. Tetrahedral coordination geometries are retained in the mutants at position 106. The mutants with Ala-106 and Gln-106 have a zinc-bound sulfate ion, whereas this sulfate site is only partially occupied in the mutant with Asp-106. The hydrogen-bond network seems to be "reversed" in the mutants with Ala-106 and Gln-106. The network is preserved as in native enzyme in the mutant with Asp-106 but the side chain of Asp-106 is more extended than that of Glu-106 in the native enzyme. These results illustrate the importance of Glu-106 and Thr-199 for controlling the precise coordination geometry of the zinc ion and its ligand preferences which results in an optimal orientation of a zinc-bound hydroxide ion for an attack on the CO2 substrate.

Structural analysis of the zinc hydroxide-Thr-199-Glu-106 hydrogen-bond network in human carbonic anhydrase II.,Xue Y, Liljas A, Jonsson BH, Lindskog S Proteins. 1993 Sep;17(1):93-106. PMID:7901850^[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
↑ Xue Y, Liljas A, Jonsson BH, Lindskog S. Structural analysis of the zinc hydroxide-Thr-199-Glu-106 hydrogen-bond network in human carbonic anhydrase II. Proteins. 1993 Sep;17(1):93-106. PMID:7901850 doi:http://dx.doi.org/10.1002/prot.340170112

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1cal"

@@ Line 1: / Line 1: @@
 ==STRUCTURAL ANALYSIS OF THE ZINC HYDROXIDE-THR 199-GLU 106 HYDROGEN BONDING NETWORK IN HUMAN CARBONIC ANHYDRASE II==
-<StructureSection load='1cal' size='340' side='right' caption='[[1cal]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+<StructureSection load='1cal' size='340' side='right'caption='[[1cal]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1cal]] 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=1CAL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1CAL FirstGlance]. <br>
@@ Line 16: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ca/1cal_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ca/1cal_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 31: / Line 31: @@
 </div>
 <div class="pdbe-citations 1cal" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
 == References ==
 <references/>
@@ Line 37: / Line 40: @@
 [[Category: Carbonate dehydratase]]
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Jonsson, B H]]
 [[Category: Liljas, A]]
 [[Category: Lindskog, S]]
 [[Category: Xue, Y]]

1cal

From Proteopedia

Revision as of 06:47, 10 October 2019

STRUCTURAL ANALYSIS OF THE ZINC HYDROXIDE-THR 199-GLU 106 HYDROGEN BONDING NETWORK IN HUMAN CARBONIC ANHYDRASE II

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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