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| | <StructureSection load='1ru0' size='340' side='right'caption='[[1ru0]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='1ru0' size='340' side='right'caption='[[1ru0]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1ru0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RU0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1RU0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1ru0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RU0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RU0 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DCOHM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/4a-hydroxytetrahydrobiopterin_dehydratase 4a-hydroxytetrahydrobiopterin dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.96 4.2.1.96] </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=1ru0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ru0 OCA], [https://pdbe.org/1ru0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ru0 RCSB], [https://www.ebi.ac.uk/pdbsum/1ru0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ru0 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=1ru0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ru0 OCA], [http://pdbe.org/1ru0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ru0 RCSB], [http://www.ebi.ac.uk/pdbsum/1ru0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ru0 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PHS2_MOUSE PHS2_MOUSE]] Involved in tetrahydrobiopterin biosynthesis. Seems to both prevent the formation of 7-pterins and accelerate the formation of quinonoid-BH2 (By similarity). Regulates the dimerization of homeodomain protein HNF-1-alpha and enhances its transcriptional activity. | + | [https://www.uniprot.org/uniprot/PHS2_MOUSE PHS2_MOUSE] Involved in tetrahydrobiopterin biosynthesis. Seems to both prevent the formation of 7-pterins and accelerate the formation of quinonoid-BH2 (By similarity). Regulates the dimerization of homeodomain protein HNF-1-alpha and enhances its transcriptional activity. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 4a-hydroxytetrahydrobiopterin dehydratase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Alber, T]] | + | [[Category: Alber T]] |
| - | [[Category: Bayle, J H]] | + | [[Category: Bayle JH]] |
| - | [[Category: Crabtree, G R]] | + | [[Category: Crabtree GR]] |
| - | [[Category: Pullen, K E]] | + | [[Category: Pullen KE]] |
| - | [[Category: Rose, R B]] | + | [[Category: Rose RB]] |
| - | [[Category: Alpha and beta structure]]
| + | |
| - | [[Category: Lyase]]
| + | |
| Structural highlights
Function
PHS2_MOUSE Involved in tetrahydrobiopterin biosynthesis. Seems to both prevent the formation of 7-pterins and accelerate the formation of quinonoid-BH2 (By similarity). Regulates the dimerization of homeodomain protein HNF-1-alpha and enhances its transcriptional activity.
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
An inherited form of diabetes, maturity-onset diabetes of the young type 3 (MODY3), results from mutations in the transcriptional activator, hepatocyte nuclear factor-1alpha (HNF1alpha). Transcription by HNF1alpha is stimulated by the bifunctional coactivator DCoH (dimerization cofactor of HNF1). Strikingly, an HNF1alpha deletion in mice causes more severe phenotypes than a DCoH deletion. It has been hypothesized that a DCoH homolog, DCoH2, partially complements the DCoH deletion. To test this idea, we determined the biochemical properties and the 1.6-A-resolution crystal structure of DCoH2. Like DCoH, DCoH2 forms a tetramer, displays pterin-4alpha-carbinolamine dehydratase activity, and binds HNF1alpha in vivo and in vitro. DCoH and DCoH2 adopt identical folds with structural differences confined largely to the protein surfaces and the tetramer interface. In contrast to the hyperstable DCoH tetramer, DCoH2 readily disproportionates and forms a 2:2 complex with HNF1 in vitro. Phylogenetic analysis reveals six major subfamilies of DCoH proteins, including unique DCoH and DCoH2 branches in metazoans. These results suggest distinct roles for DCoH and DCoH2. Differences in conserved surface residues could mediate binding to different effectors. We propose that HNF1alpha binding kinetics may distinguish regulation by DCoH2, under thermodynamic control, from regulation by DCoH, under kinetic control.
Biochemical and structural basis for partially redundant enzymatic and transcriptional functions of DCoH and DCoH2.,Rose RB, Pullen KE, Bayle JH, Crabtree GR, Alber T Biochemistry. 2004 Jun 15;43(23):7345-55. PMID:15182178[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rose RB, Pullen KE, Bayle JH, Crabtree GR, Alber T. Biochemical and structural basis for partially redundant enzymatic and transcriptional functions of DCoH and DCoH2. Biochemistry. 2004 Jun 15;43(23):7345-55. PMID:15182178 doi:10.1021/bi049620t
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