5kx5: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal structure of tubulin-stathmin-TTL-Compound 11 complex== | |||
<StructureSection load='5kx5' size='340' side='right' caption='[[5kx5]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5kx5]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Ovis_aries Ovis aries]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KX5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KX5 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6YK:(2~{S},4~{R})-4-[[2-[(1~{R},3~{R})-1-acetyloxy-3-[[(2~{S},3~{S})-2-[[(2~{R})-1,2-dimethylpyrrolidin-2-yl]carbonylamino]-3-methyl-pentanoyl]-methyl-amino]-4-methyl-pentyl]-1,3-thiazol-4-yl]carbonylamino]-5-(4-aminophenyl)-2-methyl-pentanoic+acid'>6YK</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=5kx5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kx5 OCA], [http://pdbe.org/5kx5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kx5 RCSB], [http://www.ebi.ac.uk/pdbsum/5kx5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kx5 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/D0VWZ0_SHEEP D0VWZ0_SHEEP]] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).[RuleBase:RU003505][SAAS:SAAS023123_004_019801] [[http://www.uniprot.org/uniprot/STMN4_RAT STMN4_RAT]] Exhibits microtubule-destabilizing activity.<ref>PMID:15039434</ref> <ref>PMID:12111843</ref> <ref>PMID:15014504</ref> [[http://www.uniprot.org/uniprot/D0VWY9_SHEEP D0VWY9_SHEEP]] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).[RuleBase:RU003505] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The tubulysin class of natural products has attracted much attention from the medicinal chemistry community due to its potent cytotoxicity against a wide range of human cancer cell lines, including significant activity in multidrug-resistant carcinoma models. As a result of their potency, the tubulysins have become an important tool for use in targeted therapy, being widely pursued as payloads in the development of novel small molecule drug conjugates (SMDCs) and antibody-drug conjugates (ADCs). A structure-based and parallel medicinal chemistry approach was applied to the synthesis of novel tubulysin analogues. These efforts led to the discovery of a number of novel and potent cytotoxic tubulysin analogues, providing a framework for our simultaneous report, which highlights the discovery of tubulysin-based ADCs, including use of site-specific conjugation to address in vivo stability of the C-11 acetate functionality. | |||
Design, Synthesis, and Cytotoxic Evaluation of Novel Tubulysin Analogues as ADC Payloads.,Leverett CA, Sukuru SC, Vetelino BC, Musto S, Parris K, Pandit J, Loganzo F, Varghese AH, Bai G, Liu B, Liu D, Hudson S, Doppalapudi VR, Stock J, O'Donnell CJ, Subramanyam C ACS Med Chem Lett. 2016 Aug 26;7(11):999-1004. eCollection 2016 Nov 10. PMID:27882198<ref>PMID:27882198</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5kx5" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Ovis aries]] | |||
[[Category: Parris, K]] | [[Category: Parris, K]] | ||
[[Category: Structural protein-inhibitor complex]] | |||
[[Category: Tubulin tubulysin]] | |||
Revision as of 19:15, 2 January 2017
Crystal structure of tubulin-stathmin-TTL-Compound 11 complexCrystal structure of tubulin-stathmin-TTL-Compound 11 complex
Structural highlights
Function[D0VWZ0_SHEEP] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).[RuleBase:RU003505][SAAS:SAAS023123_004_019801] [STMN4_RAT] Exhibits microtubule-destabilizing activity.[1] [2] [3] [D0VWY9_SHEEP] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).[RuleBase:RU003505] Publication Abstract from PubMedThe tubulysin class of natural products has attracted much attention from the medicinal chemistry community due to its potent cytotoxicity against a wide range of human cancer cell lines, including significant activity in multidrug-resistant carcinoma models. As a result of their potency, the tubulysins have become an important tool for use in targeted therapy, being widely pursued as payloads in the development of novel small molecule drug conjugates (SMDCs) and antibody-drug conjugates (ADCs). A structure-based and parallel medicinal chemistry approach was applied to the synthesis of novel tubulysin analogues. These efforts led to the discovery of a number of novel and potent cytotoxic tubulysin analogues, providing a framework for our simultaneous report, which highlights the discovery of tubulysin-based ADCs, including use of site-specific conjugation to address in vivo stability of the C-11 acetate functionality. Design, Synthesis, and Cytotoxic Evaluation of Novel Tubulysin Analogues as ADC Payloads.,Leverett CA, Sukuru SC, Vetelino BC, Musto S, Parris K, Pandit J, Loganzo F, Varghese AH, Bai G, Liu B, Liu D, Hudson S, Doppalapudi VR, Stock J, O'Donnell CJ, Subramanyam C ACS Med Chem Lett. 2016 Aug 26;7(11):999-1004. eCollection 2016 Nov 10. PMID:27882198[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||