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6h6s

From Proteopedia

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Current revision

Sad phasing on nickel-substituted human carbonic anhydrase II

Structural highlights

6h6s is a 2 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

Partial symmetry, i.e., the presence of more than one molecule in the asymmetric unit of a crystal, is a relatively rare phenomenon in small-molecule crystallography, but is quite common in protein crystallography, where it is typically known as non-crystallographic symmetry (NCS). Several papers in literature propose molecular determinants such as crystal contacts, thermal factors, or TLS parameters as an explanation for the phenomenon of intrinsic asymmetry among molecules that are in principle equivalent. Nevertheless, are all of the above determinants the cause or are they rather the effect? In the general frame of the NCS often observed in crystals of biomolecules, this paper deals with nickel(II)-substituted human carbonic anhydrase(II) (hCAII) and its SAD structure determination at the nickel edge. The structure revealed two non-equivalent molecules in the asymmetric unit, the presence of a secondary nickel-binding site at the N-terminus of both molecules (which had never been found before in the nickel-substituted enzyme) and two different coordination geometries of the active site nickel (hexa-coordinated in one molecule and mainly penta-coordinated in the other). The above-mentioned standard molecular crystallographic determinants of this asymmetry are analyzed and presented in detail for this particular case. From these considerations, we speculate on the existence of a fundamental, although yet unknown, common cause for the partial symmetry that is so often encountered in X-ray structures of biomolecules.

Non-crystallographic symmetry in proteins: Jahn-Teller-like and Butterfly-like effects?,Silva JM, Giuntini S, Cerofolini L, Geraldes CFGC, Macedo AL, Ravera E, Fragai M, Luchinat C, Calderone V J Biol Inorg Chem. 2018 Nov 23. pii: 10.1007/s00775-018-1630-0. doi:, 10.1007/s00775-018-1630-0. PMID:30470900^[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
↑ Silva JM, Giuntini S, Cerofolini L, Geraldes CFGC, Macedo AL, Ravera E, Fragai M, Luchinat C, Calderone V. Non-crystallographic symmetry in proteins: Jahn-Teller-like and Butterfly-like effects? J Biol Inorg Chem. 2018 Nov 23. pii: 10.1007/s00775-018-1630-0. doi:, 10.1007/s00775-018-1630-0. PMID:30470900 doi:http://dx.doi.org/10.1007/s00775-018-1630-0

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/6h6s"

@@ Line 1: / Line 1: @@
 ==Sad phasing on nickel-substituted human carbonic anhydrase II==
-<StructureSection load='6h6s' size='340' side='right' caption='[[6h6s]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
+<StructureSection load='6h6s' size='340' side='right'caption='[[6h6s]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6h6s]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6H6S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H6S FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6h6s]] is a 2 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=6H6S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H6S FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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=6h6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h6s OCA], [http://pdbe.org/6h6s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h6s RCSB], [http://www.ebi.ac.uk/pdbsum/6h6s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h6s ProSAT]</span></td></tr>
@@ Line 21: / Line 22: @@
 </div>
 <div class="pdbe-citations 6h6s" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]]
 == References ==
 <references/>
@@ Line 26: / Line 30: @@
 </StructureSection>
 [[Category: Carbonate dehydratase]]
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Calderone, V]]
 [[Category: Cerofolini, L]]

6h6s

From Proteopedia

Current revision

Sad phasing on nickel-substituted human carbonic anhydrase II

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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