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| | <StructureSection load='3rul' size='340' side='right'caption='[[3rul]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='3rul' size='340' side='right'caption='[[3rul]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3rul]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RUL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RUL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3rul]] is a 8 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=3RUL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RUL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=M12:10-METHYLUNDECANOIC+ACID'>M12</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=N1L:2-AMINO-2-DEOXY-BETA-D-GLUCOPYRANURONIC+ACID'>N1L</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</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]] 2.5Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CCS:CARBOXYMETHYLATED+CYSTEINE'>CCS</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DTY:D-TYROSINE'>DTY</scene>, <scene name='pdbligand=GHP:(2R)-AMINO(4-HYDROXYPHENYL)ETHANOIC+ACID'>GHP</scene>, <scene name='pdbligand=HCL:(2S)-2-AZANYL-2-[2-CHLORANYL-3,5-BIS(OXIDANYL)PHENYL]ETHANOIC+ACID'>HCL</scene>, <scene name='pdbligand=HG7:(2S)-2-AZANYL-N-[3-(DIMETHYLAMINO)PROPYL]-2-(3-HYDROXYPHENYL)ETHANAMIDE'>HG7</scene>, <scene name='pdbligand=HGM:(2R)-2-(4-HYDROXYPHENYL)-2-(METHYLAMINO)ETHANOIC+ACID'>HGM</scene>, <scene name='pdbligand=OMY:(BETAR)-3-CHLORO-BETA-HYDROXY-L-TYROSINE'>OMY</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CCS:CARBOXYMETHYLATED+CYSTEINE'>CCS</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DTY:D-TYROSINE'>DTY</scene>, <scene name='pdbligand=GHP:(2R)-AMINO(4-HYDROXYPHENYL)ETHANOIC+ACID'>GHP</scene>, <scene name='pdbligand=HCL:(2S)-2-AZANYL-2-[2-CHLORANYL-3,5-BIS(OXIDANYL)PHENYL]ETHANOIC+ACID'>HCL</scene>, <scene name='pdbligand=HG7:(2S)-2-AZANYL-N-[3-(DIMETHYLAMINO)PROPYL]-2-(3-HYDROXYPHENYL)ETHANAMIDE'>HG7</scene>, <scene name='pdbligand=HGM:(2R)-2-(4-HYDROXYPHENYL)-2-(METHYLAMINO)ETHANOIC+ACID'>HGM</scene>, <scene name='pdbligand=M12:10-METHYLUNDECANOIC+ACID'>M12</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=N1L:2-AMINO-2-DEOXY-BETA-D-GLUCOPYRANURONIC+ACID'>N1L</scene>, <scene name='pdbligand=OMY:(BETAR)-3-CHLORO-BETA-HYDROXY-L-TYROSINE'>OMY</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3a9j|3a9j]], [[3rum|3rum]], [[3run|3run]]</div></td></tr> | + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBC ([https://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=3rul FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rul OCA], [https://pdbe.org/3rul PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rul RCSB], [https://www.ebi.ac.uk/pdbsum/3rul PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rul ProSAT]</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=3rul FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rul OCA], [https://pdbe.org/3rul PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rul RCSB], [https://www.ebi.ac.uk/pdbsum/3rul PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rul ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/UBC_HUMAN UBC_HUMAN]] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.<ref>PMID:16543144</ref> <ref>PMID:19754430</ref>
| + | [https://www.uniprot.org/uniprot/UBC_HUMAN UBC_HUMAN] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.<ref>PMID:16543144</ref> <ref>PMID:19754430</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Economou, N J]] | + | [[Category: Economou NJ]] |
| - | [[Category: Grasty, K C]] | + | [[Category: Grasty KC]] |
| - | [[Category: Loll, P J]] | + | [[Category: Loll PJ]] |
| - | [[Category: Nahoum, V]] | + | [[Category: Nahoum V]] |
| - | [[Category: Weeks, S D]] | + | [[Category: Weeks SD]] |
| - | [[Category: Antibiotic]]
| + | |
| - | [[Category: Carboxymethylation of cysteine]]
| + | |
| - | [[Category: Dalbavancin]]
| + | |
| - | [[Category: Fusion]]
| + | |
| - | [[Category: Glycopeptide]]
| + | |
| - | [[Category: Native protein ligation]]
| + | |
| - | [[Category: Signaling protein-antibiotic complex]]
| + | |
| Structural highlights
3rul is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.5Å |
| Ligands: | , , , , , , , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
UBC_HUMAN Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.[1] [2]
Publication Abstract from PubMed
Many large natural product antibiotics act by specifically binding and sequestering target molecules found on bacterial cells. We have developed a new strategy to expedite the structural analysis of such antibiotic-target complexes, in which we covalently link the target molecules to carrier proteins, and then crystallize the entire carrier-target-antibiotic complex. Using native chemical ligation, we have linked the Lys-D-Ala-D-Ala binding epitope for glycopeptide antibiotics to three different carrier proteins. We show that recognition of this peptide by multiple antibiotics is not compromised by the presence of the carrier protein partner, and use this approach to determine the first-ever crystal structure for the new therapeutic dalbavancin. We also report the first crystal structure of an asymmetric ristocetin antibiotic dimer, as well as the structure of vancomycin bound to a carrier-target fusion. The dalbavancin structure reveals an antibiotic molecule that has closed around its binding partner; it also suggests mechanisms by which the drug can enhance its half-life by binding to serum proteins, and be targeted to bacterial membranes. Notably, the carrier protein approach is not limited to peptide ligands such as Lys-D-Ala-D-Ala, but is applicable to a diverse range of targets. This strategy is likely to yield structural insights that accelerate new therapeutic development.
A carrier protein strategy yields the structure of dalbavancin.,Economou NJ, Nahoum V, Weeks SD, Grasty KC, Zentner IJ, Townsend TM, Bhuiya MW, Cocklin S, Loll PJ J Am Chem Soc. 2012 Mar 14;134(10):4637-45. Epub 2012 Mar 1. PMID:22352468[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Huang F, Kirkpatrick D, Jiang X, Gygi S, Sorkin A. Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. Mol Cell. 2006 Mar 17;21(6):737-48. PMID:16543144 doi:S1097-2765(06)00120-1
- ↑ Komander D. The emerging complexity of protein ubiquitination. Biochem Soc Trans. 2009 Oct;37(Pt 5):937-53. doi: 10.1042/BST0370937. PMID:19754430 doi:10.1042/BST0370937
- ↑ Economou NJ, Nahoum V, Weeks SD, Grasty KC, Zentner IJ, Townsend TM, Bhuiya MW, Cocklin S, Loll PJ. A carrier protein strategy yields the structure of dalbavancin. J Am Chem Soc. 2012 Mar 14;134(10):4637-45. Epub 2012 Mar 1. PMID:22352468 doi:10.1021/ja208755j
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