4yem: Difference between revisions

New page: ==Carboplatin binding to HEWL in NaBr crystallisation conditions studied at an X-ray wavelength of 0.9163A - new refinement== <StructureSection load='4yem' size='340' side='right' caption=...
 
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==Carboplatin binding to HEWL in NaBr crystallisation conditions studied at an X-ray wavelength of 0.9163A - new refinement==
==Carboplatin binding to HEWL in NaBr crystallisation conditions studied at an X-ray wavelength of 0.9163A - new refinement==
<StructureSection load='4yem' size='340' side='right' caption='[[4yem]], [[Resolution|resolution]] 1.47&Aring;' scene=''>
<StructureSection load='4yem' size='340' side='right'caption='[[4yem]], [[Resolution|resolution]] 1.47&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4yem]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YEM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YEM FirstGlance]. <br>
<table><tr><td colspan='2'>[[4yem]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YEM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YEM FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PT:PLATINUM+(II)+ION'>PT</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]] 1.47&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xan|4xan]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PT:PLATINUM+(II)+ION'>PT</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=4yem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yem OCA], [https://pdbe.org/4yem PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yem RCSB], [https://www.ebi.ac.uk/pdbsum/4yem PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yem ProSAT]</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=4yem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yem OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4yem RCSB], [http://www.ebi.ac.uk/pdbsum/4yem PDBsum]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/LYSC_CHICK 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.<ref>PMID:22044478</ref>
[https://www.uniprot.org/uniprot/LYSC_CHICK 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.<ref>PMID:22044478</ref>  
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<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
Carboplatin is a second-generation platinum anticancer agent used for the treatment of a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine (in hen egg-white lysozyme; HEWL) showed the partial conversion of carboplatin to cisplatin owing to the high NaCl concentration used in the crystallization conditions. HEWL co-crystallizations with carboplatin in NaBr conditions have now been carried out to confirm whether carboplatin converts to the bromine form and whether this takes place in a similar way to the partial conversion of carboplatin to cisplatin observed previously in NaCl conditions. Here, it is reported that a partial chemical transformation takes place but to a transplatin form. Thus, to attempt to resolve purely carboplatin binding at histidine, this study utilized co-crystallization of HEWL with carboplatin without NaCl to eliminate the partial chemical conversion of carboplatin. Tetragonal HEWL crystals co-crystallized with carboplatin were successfully obtained in four different conditions, each at a different pH value. The structural results obtained show carboplatin bound to either one or both of the N atoms of His15 of HEWL, and this particular variation was dependent on the concentration of anions in the crystallization mixture and the elapsed time, as well as the pH used. The structural details of the bound carboplatin molecule also differed between them. Overall, the most detailed crystal structure showed the majority of the carboplatin atoms bound to the platinum centre; however, the four-carbon ring structure of the cyclobutanedicarboxylate moiety (CBDC) remained elusive. The potential impact of the results for the administration of carboplatin as an anticancer agent are described.
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.


Carboplatin binding to histidine.,Tanley SW, Diederichs K, Kroon-Batenburg LM, Levy C, Schreurs AM, Helliwell JR Acta Crystallogr F Struct Biol Commun. 2014 Sep 1;70(Pt 9):1135-42. doi:, 10.1107/S2053230X14016161. Epub 2014 Aug 29. PMID:25195881<ref>PMID:25195881</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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
<div class="pdbe-citations 4yem" style="background-color:#fffaf0;"></div>
==See Also==
*[[Lysozyme 3D structures|Lysozyme 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Gallus gallus]]
[[Category: Gallus gallus]]
[[Category: Lysozyme]]
[[Category: Large Structures]]
[[Category: Dauter, Z]]
[[Category: Dauter Z]]
[[Category: Jaskolski, M]]
[[Category: Jaskolski M]]
[[Category: Minor, W]]
[[Category: Minor W]]
[[Category: Shabalin, I G]]
[[Category: Shabalin IG]]
[[Category: Wlodawer, A]]
[[Category: Wlodawer A]]
[[Category: Carboplatin]]
[[Category: Hydrolase]]
[[Category: Metal binding]]
[[Category: Re-refinement of 4xan]]

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