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| | <StructureSection load='1jlj' size='340' side='right'caption='[[1jlj]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='1jlj' size='340' side='right'caption='[[1jlj]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1jlj]] is a 3 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=1JLJ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1JLJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1jlj]] is a 3 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=1JLJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JLJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1di6|1di6]], [[1di7|1di7]], [[1ihc|1ihc]], [[1g8r|1g8r]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GEPHYRIN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1jlj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jlj OCA], [https://pdbe.org/1jlj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jlj RCSB], [https://www.ebi.ac.uk/pdbsum/1jlj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jlj ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1jlj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jlj OCA], [http://pdbe.org/1jlj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1jlj RCSB], [http://www.ebi.ac.uk/pdbsum/1jlj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1jlj ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/GEPH_HUMAN GEPH_HUMAN]] Defects in GPHN are the cause of molybdenum cofactor deficiency type C (MOCOD type C) [MIM:[http://omim.org/entry/252150 252150]]. MOCOD type C is an autosomal recessive disease which leads to the pleiotropic loss of all molybdoenzyme activities and is characterized by severe neurological damage, neonatal seizures and early childhood death.<ref>PMID:11095995</ref> | + | [https://www.uniprot.org/uniprot/GEPH_HUMAN GEPH_HUMAN] Defects in GPHN are the cause of molybdenum cofactor deficiency type C (MOCOD type C) [MIM:[https://omim.org/entry/252150 252150]. MOCOD type C is an autosomal recessive disease which leads to the pleiotropic loss of all molybdoenzyme activities and is characterized by severe neurological damage, neonatal seizures and early childhood death.<ref>PMID:11095995</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GEPH_HUMAN GEPH_HUMAN]] Microtubule-associated protein involved in membrane protein-cytoskeleton interactions. It is thought to anchor the inhibitory glycine receptor (GLYR) to subsynaptic microtubules (By similarity). Catalyzes two steps in the biosynthesis of the molybdenum cofactor. In the first step, molybdopterin is adenylated. Subsequently, molybdate is inserted into adenylated molybdopterin and AMP is released. | + | [https://www.uniprot.org/uniprot/GEPH_HUMAN GEPH_HUMAN] Microtubule-associated protein involved in membrane protein-cytoskeleton interactions. It is thought to anchor the inhibitory glycine receptor (GLYR) to subsynaptic microtubules (By similarity). Catalyzes two steps in the biosynthesis of the molybdenum cofactor. In the first step, molybdopterin is adenylated. Subsequently, molybdate is inserted into adenylated molybdopterin and AMP is released. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 1jlj" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 1jlj" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Gephyrin|Gephyrin]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hecht, H J]] | + | [[Category: Hecht H-J]] |
| - | [[Category: Mendel, R R]] | + | [[Category: Mendel RR]] |
| - | [[Category: Schindelin, H]] | + | [[Category: Schindelin H]] |
| - | [[Category: Schrader, N]] | + | [[Category: Schrader N]] |
| - | [[Category: Schwarz, G]] | + | [[Category: Schwarz G]] |
| - | [[Category: Globular alpha/beta fold]]
| + | |
| - | [[Category: Structural protein]]
| + | |
| Structural highlights
Disease
GEPH_HUMAN Defects in GPHN are the cause of molybdenum cofactor deficiency type C (MOCOD type C) [MIM:252150. MOCOD type C is an autosomal recessive disease which leads to the pleiotropic loss of all molybdoenzyme activities and is characterized by severe neurological damage, neonatal seizures and early childhood death.[1]
Function
GEPH_HUMAN Microtubule-associated protein involved in membrane protein-cytoskeleton interactions. It is thought to anchor the inhibitory glycine receptor (GLYR) to subsynaptic microtubules (By similarity). Catalyzes two steps in the biosynthesis of the molybdenum cofactor. In the first step, molybdopterin is adenylated. Subsequently, molybdate is inserted into adenylated molybdopterin and AMP is released.
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
The molybdenum cofactor (Moco) consists of a unique and conserved pterin derivative, usually referred to as molybdopterin (MPT), which coordinates the essential transition metal molybdenum (Mo). Moco is required for the enzymatic activities of all Mo-enzymes, with the exception of nitrogenase and is synthesized by an evolutionary old multi-step pathway that is dependent on the activities of at least six gene products. In eukaryotes, the final step of Moco biosynthesis, i.e. transfer and insertion of Mo into MPT, is catalyzed by the two-domain proteins Cnx1 in plants and gephyrin in mammals. Gephyrin is ubiquitously expressed, and was initially found in the central nervous system, where it is essential for clustering of inhibitory neuroreceptors in the postsynaptic membrane. Gephyrin and Cnx1 contain at least two functional domains (E and G) that are homologous to the Escherichia coli proteins MoeA and MogA, the atomic structures of which have been solved recently. Here, we present the crystal structures of the N-terminal human gephyrin G domain (Geph-G) and the C-terminal Arabidopsis thaliana Cnx1 G domain (Cnx1-G) at 1.7 and 2.6 A resolution, respectively. These structures are highly similar and compared to MogA reveal four major differences in their three-dimensional structures: (1) In Geph-G and Cnx1-G an additional alpha-helix is present between the first beta-strand and alpha-helix of MogA. (2) The loop between alpha 2 and beta 2 undergoes conformational changes in all three structures. (3) A beta-hairpin loop found in MogA is absent from Geph-G and Cnx1-G. (4) The C terminus of Geph-G follows a different path from that in MogA. Based on the structures of the eukaryotic proteins and their comparisons with E. coli MogA, the predicted binding site for MPT has been further refined. In addition, the characterized alternative splice variants of gephyrin are analyzed in the context of the three-dimensional structure of Geph-G.
Crystal structures of human gephyrin and plant Cnx1 G domains: comparative analysis and functional implications.,Schwarz G, Schrader N, Mendel RR, Hecht HJ, Schindelin H J Mol Biol. 2001 Sep 14;312(2):405-18. PMID:11554796[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Reiss J, Gross-Hardt S, Christensen E, Schmidt P, Mendel RR, Schwarz G. A mutation in the gene for the neurotransmitter receptor-clustering protein gephyrin causes a novel form of molybdenum cofactor deficiency. Am J Hum Genet. 2001 Jan;68(1):208-13. Epub 2000 Nov 28. PMID:11095995 doi:10.1086/316941
- ↑ Schwarz G, Schrader N, Mendel RR, Hecht HJ, Schindelin H. Crystal structures of human gephyrin and plant Cnx1 G domains: comparative analysis and functional implications. J Mol Biol. 2001 Sep 14;312(2):405-18. PMID:11554796 doi:10.1006/jmbi.2001.4952
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