4cvh: Difference between revisions
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<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. 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> | </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://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]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/ISPD_HUMAN 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.<ref>PMID:22522420</ref> <ref>PMID:22522421</ref> | [[http://www.uniprot.org/uniprot/ISPD_HUMAN 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.<ref>PMID:22522420</ref> <ref>PMID:22522421</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:26687144</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4cvh" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 15:20, 13 January 2016
Crystal structure of human isoprenoid synthase domain-containing proteinCrystal structure of human isoprenoid synthase domain-containing protein
Structural highlights
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 PubMedA 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
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