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| | ==Crystal structure of human Orc6 fragment== | | ==Crystal structure of human Orc6 fragment== |
| - | <StructureSection load='3m03' size='340' side='right' caption='[[3m03]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='3m03' size='340' side='right'caption='[[3m03]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3m03]] 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=3M03 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3M03 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3m03]] 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=3M03 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3M03 FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ORC6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3m03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m03 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3m03 RCSB], [http://www.ebi.ac.uk/pdbsum/3m03 PDBsum]</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=3m03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m03 OCA], [https://pdbe.org/3m03 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3m03 RCSB], [https://www.ebi.ac.uk/pdbsum/3m03 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3m03 ProSAT]</span></td></tr> |
| - | <table> | + | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/ORC6_HUMAN ORC6_HUMAN]] Ear-patella-short stature syndrome. Defects in ORC6 are the cause of Meier-Gorlin syndrome type 3 (MGORS3) [MIM:[http://omim.org/entry/613803 613803]]. MGORS3 is a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal.<ref>PMID:21358632</ref> | + | [https://www.uniprot.org/uniprot/ORC6_HUMAN ORC6_HUMAN] Ear-patella-short stature syndrome. Defects in ORC6 are the cause of Meier-Gorlin syndrome type 3 (MGORS3) [MIM:[https://omim.org/entry/613803 613803]. MGORS3 is a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal.<ref>PMID:21358632</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ORC6_HUMAN ORC6_HUMAN]] Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent, however specific DNA sequences that define origins of replication have not been identified so far. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication. | + | [https://www.uniprot.org/uniprot/ORC6_HUMAN ORC6_HUMAN] Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent, however specific DNA sequences that define origins of replication have not been identified so far. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | Structural analysis of human Orc6 protein reveals a homology with transcription factor TFIIB.,Liu S, Balasov M, Wang H, Wu L, Chesnokov IN, Liu Y Proc Natl Acad Sci U S A. 2011 Apr 18. PMID:21502537<ref>PMID:21502537</ref> | | Structural analysis of human Orc6 protein reveals a homology with transcription factor TFIIB.,Liu S, Balasov M, Wang H, Wu L, Chesnokov IN, Liu Y Proc Natl Acad Sci U S A. 2011 Apr 18. PMID:21502537<ref>PMID:21502537</ref> |
| | | | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3m03" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Liu, S X.]] | + | [[Category: Large Structures]] |
| - | [[Category: Liu, Y F.]] | + | [[Category: Liu SX]] |
| - | [[Category: Sun, J.]] | + | [[Category: Liu YF]] |
| - | [[Category: Wang, H F.]] | + | [[Category: Sun J]] |
| - | [[Category: Wu, L J.]]
| + | [[Category: Wang HF]] |
| - | [[Category: Dna binding protein]] | + | [[Category: Wu LJ]] |
| - | [[Category: Dna replication]] | + | |
| - | [[Category: Helix turn helix]]
| + | |
| - | [[Category: Origin recognition complex]]
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| Structural highlights
Disease
ORC6_HUMAN Ear-patella-short stature syndrome. Defects in ORC6 are the cause of Meier-Gorlin syndrome type 3 (MGORS3) [MIM:613803. MGORS3 is a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal.[1]
Function
ORC6_HUMAN Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent, however specific DNA sequences that define origins of replication have not been identified so far. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication.
Publication Abstract from PubMed
The Origin Recognition Complex (ORC) is a six-subunit protein important for the initiation of DNA replication in eukaryotic cells. Orc6 is the smallest and the least conserved among ORC subunits. It is required for the DNA replication but also has a function in cytokinesis in metazoan species, however, the mechanisms of Orc6 action in these processes are not clear. Here we report a structure of the middle domain of human Orc6. This domain has an overall fold similar to the corresponding helical domain of transcription factor TFIIB. Based on these findings, a model of Orc6 binding to DNA is produced. We have identified amino acids of Orc6 which are directly involved in DNA binding. Alterations of these amino acids abolish DNA binding ability of Orc6 and also result in reduced levels of DNA replication in vitro and in cultured cells. Our data indicate that Orc6 is one of the DNA binding subunits of ORC in metazoan species. We propose that Orc6 may participate in positioning of ORC at the origins of DNA replication similar to the role of TFIIB in positioning transcription preinitiation complex at the promoter.
Structural analysis of human Orc6 protein reveals a homology with transcription factor TFIIB.,Liu S, Balasov M, Wang H, Wu L, Chesnokov IN, Liu Y Proc Natl Acad Sci U S A. 2011 Apr 18. PMID:21502537[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bicknell LS, Bongers EM, Leitch A, Brown S, Schoots J, Harley ME, Aftimos S, Al-Aama JY, Bober M, Brown PA, van Bokhoven H, Dean J, Edrees AY, Feingold M, Fryer A, Hoefsloot LH, Kau N, Knoers NV, Mackenzie J, Opitz JM, Sarda P, Ross A, Temple IK, Toutain A, Wise CA, Wright M, Jackson AP. Mutations in the pre-replication complex cause Meier-Gorlin syndrome. Nat Genet. 2011 Feb 27;43(4):356-9. doi: 10.1038/ng.775. PMID:21358632 doi:10.1038/ng.775
- ↑ Liu S, Balasov M, Wang H, Wu L, Chesnokov IN, Liu Y. Structural analysis of human Orc6 protein reveals a homology with transcription factor TFIIB. Proc Natl Acad Sci U S A. 2011 Apr 18. PMID:21502537 doi:10.1073/pnas.1013676108
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