m |
|
| Line 6: |
Line 6: |
| | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4g4a|4g4a]]</td></tr> | | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4g4a|4g4a]]</td></tr> |
| | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </span></td></tr> | | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4yen FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yen OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4yen RCSB], [http://www.ebi.ac.uk/pdbsum/4yen PDBsum]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4yen FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yen OCA], [http://pdbe.org/4yen PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yen RCSB], [http://www.ebi.ac.uk/pdbsum/4yen PDBsum]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| Line 12: |
Line 12: |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| - | The anticancer complexes cisplatin and carboplatin are known to bind to both the Ndelta and the N atoms of His15 of hen egg-white lysozyme (HEWL) in the presence of dimethyl sulfoxide (DMSO). However, neither binds in aqueous media after 4 d of crystallization and crystal growth, suggesting that DMSO facilitates cisplatin/carboplatin binding to the N atoms of His15 by an unknown mechanism. Crystals of HEWL cocrystallized with cisplatin in both aqueous and DMSO media, of HEWL cocrystallized with carboplatin in DMSO medium and of HEWL cocrystallized with cisplatin and N-acetylglucosamine (NAG) in DMSO medium were stored for between seven and 15 months. X-ray diffraction studies of these crystals were carried out on a Bruker APEX II home-source diffractometer at room temperature. Room-temperature X-ray diffraction data collection removed the need for cryoprotectants to be used, ruling out any effect that the cryoprotectants might have had on binding to the protein. Both cisplatin and carboplatin still bind to both the Ndelta and N atoms of His15 in DMSO media as expected, but more detail for the cyclobutanedicarboxylate (CBDC) moiety of carboplatin was observed at the N binding site. However, two molecules of cisplatin were now observed to be bound to His15 in aqueous conditions. The platinum peak positions were identified using anomalous difference electron-density maps as a cross-check with Fo-Fc OMIT electron-density maps. The occupancies of each binding site were calculated using SHELXTL. These results show that over time cisplatin binds to both N atoms of His15 of HEWL in aqueous media, whereas this binding is speeded up in the presence of DMSO. The implication of cisplatin binding to proteins after a prolonged period of time is an important consideration for the length of treatment in patients who are given cisplatin. | + | The anticancer activity of platinum-containing drugs such as cisplatin and carboplatin is considered to primarily arise from their interactions with nucleic acids; nevertheless, these drugs, or the products of their hydrolysis, also bind to proteins, potentially leading to the known side effects of the treatments. Here, over 40 crystal structures deposited in the Protein Data Bank (PDB) of cisplatin and carboplatin complexes of several proteins were analysed. Significant problems of either a crystallographic or a chemical nature were found in most of the presented atomic models and they could be traced to less or more serious deficiencies in the data-collection and refinement procedures. The re-evaluation of these data and models was possible thanks to their mandatory or voluntary deposition in publicly available databases, emphasizing the point that the availability of such data is critical for making structural science reproducible. Based on this analysis of a selected group of macromolecular structures, the importance of deposition of raw diffraction data is stressed and a procedure for depositing, tracking and using re-refined crystallographic models is suggested. |
| | | | |
| - | Room-temperature X-ray diffraction studies of cisplatin and carboplatin binding to His15 of HEWL after prolonged chemical exposure.,Tanley SW, Schreurs AM, Kroon-Batenburg LM, Helliwell JR Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Nov 1;68(Pt 11):1300-6., doi: 10.1107/S1744309112042005. Epub 2012 Oct 26. PMID:23143236<ref>PMID:23143236</ref>
| + | Crystallography and chemistry should always go together: a cautionary tale of protein complexes with cisplatin and carboplatin.,Shabalin I, Dauter Z, Jaskolski M, Minor W, Wlodawer A Acta Crystallogr D Biol Crystallogr. 2015 Sep 1;71(Pt 9):1965-79. doi:, 10.1107/S139900471500629X. Epub 2015 Aug 28. PMID:26327386<ref>PMID:26327386</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 4yen" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Structural highlights
Function
[LYSC_CHICK] Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Has bacteriolytic activity against M.luteus.[1]
Publication Abstract from PubMed
The anticancer activity of platinum-containing drugs such as cisplatin and carboplatin is considered to primarily arise from their interactions with nucleic acids; nevertheless, these drugs, or the products of their hydrolysis, also bind to proteins, potentially leading to the known side effects of the treatments. Here, over 40 crystal structures deposited in the Protein Data Bank (PDB) of cisplatin and carboplatin complexes of several proteins were analysed. Significant problems of either a crystallographic or a chemical nature were found in most of the presented atomic models and they could be traced to less or more serious deficiencies in the data-collection and refinement procedures. The re-evaluation of these data and models was possible thanks to their mandatory or voluntary deposition in publicly available databases, emphasizing the point that the availability of such data is critical for making structural science reproducible. Based on this analysis of a selected group of macromolecular structures, the importance of deposition of raw diffraction data is stressed and a procedure for depositing, tracking and using re-refined crystallographic models is suggested.
Crystallography and chemistry should always go together: a cautionary tale of protein complexes with cisplatin and carboplatin.,Shabalin I, Dauter Z, Jaskolski M, Minor W, Wlodawer A Acta Crystallogr D Biol Crystallogr. 2015 Sep 1;71(Pt 9):1965-79. doi:, 10.1107/S139900471500629X. Epub 2015 Aug 28. PMID:26327386[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Maehashi K, Matano M, Irisawa T, Uchino M, Kashiwagi Y, Watanabe T. Molecular characterization of goose- and chicken-type lysozymes in emu (Dromaius novaehollandiae): evidence for extremely low lysozyme levels in emu egg white. Gene. 2012 Jan 15;492(1):244-9. doi: 10.1016/j.gene.2011.10.021. Epub 2011 Oct, 25. PMID:22044478 doi:10.1016/j.gene.2011.10.021
- ↑ Shabalin I, Dauter Z, Jaskolski M, Minor W, Wlodawer A. Crystallography and chemistry should always go together: a cautionary tale of protein complexes with cisplatin and carboplatin. Acta Crystallogr D Biol Crystallogr. 2015 Sep 1;71(Pt 9):1965-79. doi:, 10.1107/S139900471500629X. Epub 2015 Aug 28. PMID:26327386 doi:http://dx.doi.org/10.1107/S139900471500629X
|
