4cvh

From Proteopedia

(Difference between revisions)

Revision as of 19:49, 24 January 2018

Crystal structure of human isoprenoid synthase domain-containing protein

Structural highlights

4cvh 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:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ISPD_HUMAN] Autosomal recessive limb-girdle muscular dystrophy due to ISPD deficiency;Congenital muscular dystrophy without intellectual disability;Walker-Warburg syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

Function

[ISPD_HUMAN] Required for protein O-linked mannosylation. Probably acts as a nucleotidyltransferase involved in synthesis of a nucleotide sugar. Required for dystroglycan O-mannosylation.^[1] ^[2]

Publication Abstract from PubMed

A unique, unsolved O-mannosyl glycan on alpha-dystroglycan is essential for its interaction with protein ligands in the extracellular matrix. Defective O-mannosylation leads to a group of muscular dystrophies, called dystroglycanopathies. Mutations in isoprenoid synthase domain containing (ISPD) represent the second most common cause of these disorders, however, its molecular function remains uncharacterized. The human ISPD (hISPD) crystal structure showed a canonical N-terminal cytidyltransferase domain linked to a C-terminal domain that is absent in cytidyltransferase homologs. Functional studies demonstrated cytosolic localization of hISPD, and cytidyltransferase activity toward pentose phosphates, including ribulose 5-phosphate, ribose 5-phosphate, and ribitol 5-phosphate. Identity of the CDP sugars was confirmed by liquid chromatography quadrupole time-of-flight mass spectrometry and two-dimensional nuclear magnetic resonance spectroscopy. Our combined results indicate that hISPD is a cytidyltransferase, suggesting the presence of a novel human nucleotide sugar essential for functional alpha-dystroglycan O-mannosylation in muscle and brain. Thereby, ISPD deficiency can be added to the growing list of tertiary dystroglycanopathies.

Human ISPD Is a Cytidyltransferase Required for Dystroglycan O-Mannosylation.,Riemersma M, Froese DS, van Tol W, Engelke UF, Kopec J, van Scherpenzeel M, Ashikov A, Krojer T, von Delft F, Tessari M, Buczkowska A, Swiezewska E, Jae LT, Brummelkamp TR, Manya H, Endo T, van Bokhoven H, Yue WW, Lefeber DJ Chem Biol. 2015 Dec 17;22(12):1643-52. doi: 10.1016/j.chembiol.2015.10.014. Epub , 2015 Dec 10. PMID:26687144^[3]

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

References

↑ Willer T, Lee H, Lommel M, Yoshida-Moriguchi T, de Bernabe DB, Venzke D, Cirak S, Schachter H, Vajsar J, Voit T, Muntoni F, Loder AS, Dobyns WB, Winder TL, Strahl S, Mathews KD, Nelson SF, Moore SA, Campbell KP. ISPD loss-of-function mutations disrupt dystroglycan O-mannosylation and cause Walker-Warburg syndrome. Nat Genet. 2012 May;44(5):575-80. doi: 10.1038/ng.2252. PMID:22522420 doi:http://dx.doi.org/10.1038/ng.2252
↑ Roscioli T, Kamsteeg EJ, Buysse K, Maystadt I, van Reeuwijk J, van den Elzen C, van Beusekom E, Riemersma M, Pfundt R, Vissers LE, Schraders M, Altunoglu U, Buckley MF, Brunner HG, Grisart B, Zhou H, Veltman JA, Gilissen C, Mancini GM, Delree P, Willemsen MA, Ramadza DP, Chitayat D, Bennett C, Sheridan E, Peeters EA, Tan-Sindhunata GM, de Die-Smulders CE, Devriendt K, Kayserili H, El-Hashash OA, Stemple DL, Lefeber DJ, Lin YY, van Bokhoven H. Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of alpha-dystroglycan. Nat Genet. 2012 May;44(5):581-5. doi: 10.1038/ng.2253. PMID:22522421 doi:http://dx.doi.org/10.1038/ng.2253
↑ Riemersma M, Froese DS, van Tol W, Engelke UF, Kopec J, van Scherpenzeel M, Ashikov A, Krojer T, von Delft F, Tessari M, Buczkowska A, Swiezewska E, Jae LT, Brummelkamp TR, Manya H, Endo T, van Bokhoven H, Yue WW, Lefeber DJ. Human ISPD Is a Cytidyltransferase Required for Dystroglycan O-Mannosylation. Chem Biol. 2015 Dec 17;22(12):1643-52. doi: 10.1016/j.chembiol.2015.10.014. Epub , 2015 Dec 10. PMID:26687144 doi:http://dx.doi.org/10.1016/j.chembiol.2015.10.014

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4cvh"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human isoprenoid synthase domain-containing protein==
 <StructureSection load='4cvh' size='340' side='right' caption='[[4cvh]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4cvh]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CVH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CVH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4cvh]] 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=4CVH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CVH FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=4cvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cvh OCA], [http://pdbe.org/4cvh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cvh RCSB], [http://www.ebi.ac.uk/pdbsum/4cvh PDBsum]</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=4cvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cvh OCA], [http://pdbe.org/4cvh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cvh RCSB], [http://www.ebi.ac.uk/pdbsum/4cvh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cvh ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Arrowsmith, C]]
 [[Category: Bountra, C]]

4cvh

From Proteopedia

Revision as of 19:49, 24 January 2018

Crystal structure of human isoprenoid synthase domain-containing protein

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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