2h2u

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the E130Y mutant of human soluble calcium-activated nucleotidase (SCAN) with calcium ion

Structural highlights

2h2u is a 2 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 2.4Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CANT1_HUMAN Desbuquois syndrome. The disease is caused by mutations affecting the gene represented in this entry.

Function

CANT1_HUMAN Calcium-dependent nucleotidase with a preference for UDP. The order of activity with different substrates is UDP > GDP > UTP > GTP. Has very low activity towards ADP and even lower activity towards ATP. Does not hydrolyze AMP and GMP. Involved in proteoglycan synthesis.^[1] ^[2] ^[3]

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

Mammals express a protein homologous to soluble nucleotidases used by blood-sucking insects to inhibit host blood clotting. These vertebrate nucleotidases may play a role in protein glycosylation. The activity of this enzyme family is strictly dependent on calcium, which induces a conformational change in the secreted, soluble human nucleotidase. The crystal structure of this human enzyme was recently solved; however, the mechanism of calcium activation and the basis for the calcium-induced changes remain unclear. In this study, using analytical ultracentrifugation and chemical cross-linking, we show that calcium or strontium induce noncovalent dimerization of the soluble human enzyme. The location and nature of the dimer interface was elucidated using a combination of site-directed mutagenesis and chemical cross-linking, coupled with crystallographic analyses. Replacement of Ile(170), Ser(172), and Ser(226) with cysteine residues resulted in calcium-dependent, sulfhydryl-specific intermolecular cross-linking, which was not observed after cysteine introduction at other surface locations. Analysis of a super-active mutant, E130Y, revealed that this mutant dimerized more readily than the wild-type enzyme. The crystal structure of the E130Y mutant revealed that the mutated residue is found in the dimer interface. In addition, expression of the full-length nucleotidase revealed that this membrane-bound form can also dimerize and that these dimers are stabilized by spontaneous oxidative cross-linking of Cys(30), located between the single transmembrane helix and the start of the soluble sequence. Thus, calcium-mediated dimerization may also represent a mechanism for regulation of the activity of this nucleotidase in the physiological setting of the endoplasmic reticulum or Golgi.

Calcium-dependent dimerization of human soluble calcium activated nucleotidase: characterization of the dimer interface.,Yang M, Horii K, Herr AB, Kirley TL J Biol Chem. 2006 Sep 22;281(38):28307-17. Epub 2006 Jul 11. PMID:16835225^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Smith TM, Hicks-Berger CA, Kim S, Kirley TL. Cloning, expression, and characterization of a soluble calcium-activated nucleotidase, a human enzyme belonging to a new family of extracellular nucleotidases. Arch Biochem Biophys. 2002 Oct 1;406(1):105-15. PMID:12234496
↑ Yang M, Kirley TL. Site-directed mutagenesis of human soluble calcium-activated nucleotidase 1 (hSCAN-1): identification of residues essential for enzyme activity and the Ca(2+)-induced conformational change. Biochemistry. 2004 Jul 20;43(28):9185-94. PMID:15248776 doi:http://dx.doi.org/10.1021/bi049565o
↑ Nizon M, Huber C, De Leonardis F, Merrina R, Forlino A, Fradin M, Tuysuz B, Abu-Libdeh BY, Alanay Y, Albrecht B, Al-Gazali L, Basaran SY, Clayton-Smith J, Desir J, Gill H, Greally MT, Koparir E, van Maarle MC, MacKay S, Mortier G, Morton J, Sillence D, Vilain C, Young I, Zerres K, Le Merrer M, Munnich A, Le Goff C, Rossi A, Cormier-Daire V. Further delineation of CANT1 phenotypic spectrum and demonstration of its role in proteoglycan synthesis. Hum Mutat. 2012 Aug;33(8):1261-6. doi: 10.1002/humu.22104. Epub 2012 May 22. PMID:22539336 doi:http://dx.doi.org/10.1002/humu.22104
↑ Yang M, Horii K, Herr AB, Kirley TL. Calcium-dependent dimerization of human soluble calcium activated nucleotidase: characterization of the dimer interface. J Biol Chem. 2006 Sep 22;281(38):28307-17. Epub 2006 Jul 11. PMID:16835225 doi:10.1074/jbc.M604413200

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2h2u"

@@ Line 3: / Line 3: @@
 <StructureSection load='2h2u' size='340' side='right'caption='[[2h2u]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2h2u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H2U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H2U FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2h2u]] is a 2 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=2H2U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H2U FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2h2n|2h2n]], [[1s18|1s18]], [[1s1d|1s1d]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CANT1, SHAPY ([https://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'>[https://en.wikipedia.org/wiki/Nucleoside_diphosphate_phosphatase Nucleoside diphosphate phosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.6 3.6.1.6] </span></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=2h2u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h2u OCA], [https://pdbe.org/2h2u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h2u RCSB], [https://www.ebi.ac.uk/pdbsum/2h2u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h2u ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/CANT1_HUMAN CANT1_HUMAN]] Desbuquois syndrome. The disease is caused by mutations affecting the gene represented in this entry.
+[https://www.uniprot.org/uniprot/CANT1_HUMAN CANT1_HUMAN] Desbuquois syndrome. The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[https://www.uniprot.org/uniprot/CANT1_HUMAN CANT1_HUMAN]] Calcium-dependent nucleotidase with a preference for UDP. The order of activity with different substrates is UDP > GDP > UTP > GTP. Has very low activity towards ADP and even lower activity towards ATP. Does not hydrolyze AMP and GMP. Involved in proteoglycan synthesis.<ref>PMID:12234496</ref> <ref>PMID:15248776</ref> <ref>PMID:22539336</ref>
+[https://www.uniprot.org/uniprot/CANT1_HUMAN CANT1_HUMAN] Calcium-dependent nucleotidase with a preference for UDP. The order of activity with different substrates is UDP > GDP > UTP > GTP. Has very low activity towards ADP and even lower activity towards ATP. Does not hydrolyze AMP and GMP. Involved in proteoglycan synthesis.<ref>PMID:12234496</ref> <ref>PMID:15248776</ref> <ref>PMID:22539336</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 37: / Line 35: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Nucleoside diphosphate phosphatase]]
+[[Category: Herr AB]]
-[[Category: Herr, A B]]
+[[Category: Horii K]]
-[[Category: Horii, K]]
+[[Category: Kirley TL]]
-[[Category: Kirley, T L]]
+[[Category: Yang M]]
-[[Category: Yang, M]]
-[[Category: Calcium-binding protein]]
-[[Category: Five-blade beta propeller]]
-[[Category: Hydrolase]]
-[[Category: Nucleotidase]]
-[[Category: Nucleotide-binding]]

2h2u

From Proteopedia

Current revision

Crystal structure of the E130Y mutant of human soluble calcium-activated nucleotidase (SCAN) with calcium ion

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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