2eu3: Difference between revisions

Revision as of 07:16, 24 July 2019

Human Carbonic anhydrase II in complex with novel inhibitors

Structural highlights

2eu3 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:	FF3, ZN
Related:	2eu2
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]

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

Human carbonic anhydrases (CAs) are well studied targets for the development of inhibitors for pharmaceutical applications. The crystal structure of human CA II has been determined in complex with two CA inhibitors (CAIs) containing conventional sulfonamide and thiadiazole moieties separated by a -CF2- or -CHNH2- spacer group. The structures presented here reveal that these spacer groups allow novel binding modes for the thiadiazole moiety compared with conventional CAIs.

X-ray crystallographic studies reveal that the incorporation of spacer groups in carbonic anhydrase inhibitors causes alternate binding modes.,Fisher SZ, Govindasamy L, Boyle N, Agbandje-McKenna M, Silverman DN, Blackburn GM, McKenna R Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 Jul 1;62(Pt, 7):618-22. Epub 2006 Jun 10. PMID:16820676^[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
↑ Fisher SZ, Govindasamy L, Boyle N, Agbandje-McKenna M, Silverman DN, Blackburn GM, McKenna R. X-ray crystallographic studies reveal that the incorporation of spacer groups in carbonic anhydrase inhibitors causes alternate binding modes. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 Jul 1;62(Pt, 7):618-22. Epub 2006 Jun 10. PMID:16820676 doi:https://dx.doi.org/10.1107/S1744309106020446

Proteopedia Page Contributors and Editors (what is this?)

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] Fisher SZ, Govindasamy L, Boyle N, Agbandje-McKenna M, Silverman DN, Blackburn GM, McKenna R. X-ray crystallographic studies reveal that the incorporation of spacer groups in carbonic anhydrase inhibitors causes alternate binding modes. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 Jul 1;62(Pt, 7):618-22. Epub 2006 Jun 10. PMID:16820676 doi:https://dx.doi.org/10.1107/S1744309106020446

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

@@ Line 1: / Line 1: @@
 ==Human Carbonic anhydrase II in complex with novel inhibitors==
-<StructureSection load='2eu3' size='340' side='right' caption='[[2eu3]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+<StructureSection load='2eu3' size='340' side='right'caption='[[2eu3]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2eu3]] 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=2EU3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2EU3 FirstGlance]. <br>
@@ Line 18: / Line 18: @@
 Check<jmol>
    <jmolCheckbox>
-     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eu/2eu3_consurf.spt"</scriptWhenChecked>
+     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eu/2eu3_consurf.spt"</scriptWhenChecked>
      <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
      <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 33: / Line 33: @@
 </div>
 <div class="pdbe-citations 2eu3" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
 == References ==
 <references/>
@@ Line 39: / Line 42: @@
 [[Category: Carbonate dehydratase]]
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Agbandje-McKenna, M]]
 [[Category: Blackburn, G M]]

2eu3: Difference between revisions

Revision as of 07:16, 24 July 2019

Human Carbonic anhydrase II in complex with novel inhibitors

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools