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| | <StructureSection load='3vfk' size='340' side='right'caption='[[3vfk]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='3vfk' size='340' side='right'caption='[[3vfk]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3vfk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Actinoplanes_teichomyceticus Actinoplanes teichomyceticus] and [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VFK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VFK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3vfk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Actinoplanes_teichomyceticus Actinoplanes teichomyceticus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VFK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VFK FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GCS:D-GLUCOSAMINE'>GCS</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=T55:8-METHYLNONANOIC+ACID'>T55</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]] 2.8Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=3FG:(2S)-AMINO(3,5-DIHYDROXYPHENYL)ETHANOIC+ACID'>3FG</scene>, <scene name='pdbligand=3MY:3-CHLORO-D-TYROSINE'>3MY</scene>, <scene name='pdbligand=CCS:CARBOXYMETHYLATED+CYSTEINE'>CCS</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=GHP:(2R)-AMINO(4-HYDROXYPHENYL)ETHANOIC+ACID'>GHP</scene>, <scene name='pdbligand=OMX:(BETAR)-BETA-HYDROXY-L-TYROSINE'>OMX</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3FG:(2S)-AMINO(3,5-DIHYDROXYPHENYL)ETHANOIC+ACID'>3FG</scene>, <scene name='pdbligand=3MY:3-CHLORO-D-TYROSINE'>3MY</scene>, <scene name='pdbligand=CCS:CARBOXYMETHYLATED+CYSTEINE'>CCS</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=GCS:D-GLUCOSAMINE'>GCS</scene>, <scene name='pdbligand=GHP:(2R)-AMINO(4-HYDROXYPHENYL)ETHANOIC+ACID'>GHP</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=OMX:(BETAR)-BETA-HYDROXY-L-TYROSINE'>OMX</scene>, <scene name='pdbligand=T55:8-METHYLNONANOIC+ACID'>T55</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;'>[[1jw4|1jw4]], [[3run|3run]], [[3rul|3rul]], [[3rum|3rum]], [[3vfj|3vfj]]</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=3vfk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vfk OCA], [https://pdbe.org/3vfk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vfk RCSB], [https://www.ebi.ac.uk/pdbsum/3vfk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vfk 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=3vfk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vfk OCA], [https://pdbe.org/3vfk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vfk RCSB], [https://www.ebi.ac.uk/pdbsum/3vfk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vfk 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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| | </StructureSection> | | </StructureSection> |
| | [[Category: Actinoplanes teichomyceticus]] | | [[Category: Actinoplanes teichomyceticus]] |
| - | [[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: Weeks, S D]] | + | [[Category: Weeks SD]] |
| - | [[Category: Acetylation of cyteine with iodoacetate modification]]
| + | |
| - | [[Category: Sugar binding protein-antibiotic complex]]
| + | |
| - | [[Category: Teicoplanin]]
| + | |
| Structural highlights
3vfk is a 2 chain structure with sequence from Actinoplanes teichomyceticus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.8Å |
| 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
Multidrug-resistant bacterial infections are commonly treated with glycopeptide antibiotics such as teicoplanin. This drug inhibits bacterial cell-wall biosynthesis by binding and sequestering a cell-wall precursor: a D-alanine-containing peptide. A carrier-protein strategy was used to crystallize the complex of teicoplanin and its target peptide by fusing the cell-wall peptide to either MBP or ubiquitin via native chemical ligation and subsequently crystallizing the protein-peptide-antibiotic complex. The 2.05 A resolution MBP-peptide-teicoplanin structure shows that teicoplanin recognizes its ligand through a combination of five hydrogen bonds and multiple van der Waals interactions. Comparison of this teicoplanin structure with that of unliganded teicoplanin reveals a flexibility in the antibiotic peptide backbone that has significant implications for ligand recognition. Diffraction experiments revealed an X-ray-induced dechlorination of the sixth amino acid of the antibiotic; it is shown that teicoplanin is significantly more radiation-sensitive than other similar antibiotics and that ligand binding increases radiosensitivity. Insights derived from this new teicoplanin structure may contribute to the development of next-generation antibacterials designed to overcome bacterial resistance.
Structure of the complex between teicoplanin and a bacterial cell-wall peptide: use of a carrier-protein approach.,Economou NJ, Zentner IJ, Lazo E, Jakoncic J, Stojanoff V, Weeks SD, Grasty KC, Cocklin S, Loll PJ Acta Crystallogr D Biol Crystallogr. 2013 Apr;69(Pt 4):520-33. doi:, 10.1107/S0907444912050469. Epub 2013 Mar 14. PMID:23519660[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, Zentner IJ, Lazo E, Jakoncic J, Stojanoff V, Weeks SD, Grasty KC, Cocklin S, Loll PJ. Structure of the complex between teicoplanin and a bacterial cell-wall peptide: use of a carrier-protein approach. Acta Crystallogr D Biol Crystallogr. 2013 Apr;69(Pt 4):520-33. doi:, 10.1107/S0907444912050469. Epub 2013 Mar 14. PMID:23519660 doi:10.1107/S0907444912050469
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