This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

5iyz

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Tubulin-MMAE complex

Structural highlights

5iyz is a 6 chain structure with sequence from Bos taurus, Gallus gallus and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8Å
Ligands:	, , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

STMN4_RAT Exhibits microtubule-destabilizing activity.^[1] ^[2] ^[3]

Publication Abstract from PubMed

The auristatin class of microtubule destabilizers are highly potent cytotoxic agents against several cancer cell types when delivered as antibody drug conjugates. Here we describe the high resolution structures of tubulin in complex with both monomethyl auristatin E and F and unambiguously define the trans-configuration of both ligands at the Val-Dil amide bond in their tubulin bound state. Moreover, we illustrate how peptidic vinca-site agents carrying terminal carboxylate residues may exploit an observed extended hydrogen bond network with the M-loop Arg278 to greatly improve the affinity of the corresponding analogs and to maintain the M-loop in an incompatible conformation for productive lateral tubulin-tubulin contacts in microtubules. Our results highlight a potential, previously undescribed molecular mechanism by which peptidic vinca-site agents maintain unparalleled potency as microtubule-destabilizing agents.

Structural Basis of Microtubule Destabilization by Potent Auristatin Anti-Mitotics.,Waight AB, Bargsten K, Doronina S, Steinmetz MO, Sussman D, Prota AE PLoS One. 2016 Aug 12;11(8):e0160890. doi: 10.1371/journal.pone.0160890., eCollection 2016. PMID:27518442^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Nakao C, Itoh TJ, Hotani H, Mori N. Modulation of the stathmin-like microtubule destabilizing activity of RB3, a neuron-specific member of the SCG10 family, by its N-terminal domain. J Biol Chem. 2004 May 28;279(22):23014-21. Epub 2004 Mar 22. PMID:15039434 doi:http://dx.doi.org/10.1074/jbc.M313693200
↑ Gavet O, El Messari S, Ozon S, Sobel A. Regulation and subcellular localization of the microtubule-destabilizing stathmin family phosphoproteins in cortical neurons. J Neurosci Res. 2002 Jun 1;68(5):535-50. PMID:12111843 doi:http://dx.doi.org/10.1002/jnr.10234
↑ Ravelli RB, Gigant B, Curmi PA, Jourdain I, Lachkar S, Sobel A, Knossow M. Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature. 2004 Mar 11;428(6979):198-202. PMID:15014504 doi:http://dx.doi.org/10.1038/nature02393
↑ Waight AB, Bargsten K, Doronina S, Steinmetz MO, Sussman D, Prota AE. Structural Basis of Microtubule Destabilization by Potent Auristatin Anti-Mitotics. PLoS One. 2016 Aug 12;11(8):e0160890. doi: 10.1371/journal.pone.0160890., eCollection 2016. PMID:27518442 doi:http://dx.doi.org/10.1371/journal.pone.0160890

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5iyz"

@@ Line 1: / Line 1: @@
 ==Tubulin-MMAE complex==
-<StructureSection load='5iyz' size='340' side='right' caption='[[5iyz]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+<StructureSection load='5iyz' size='340' side='right'caption='[[5iyz]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5iyz]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IYZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IYZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5iyz]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IYZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IYZ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4Q5:N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide'>4Q5</scene>, <scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</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=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.8&#8491;</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=5iyz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iyz OCA], [http://pdbe.org/5iyz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5iyz RCSB], [http://www.ebi.ac.uk/pdbsum/5iyz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5iyz ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4Q5:N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide'>4Q5</scene>, <scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</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=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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'>[https://proteopedia.org/fgij/fg.htm?mol=5iyz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iyz OCA], [https://pdbe.org/5iyz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5iyz RCSB], [https://www.ebi.ac.uk/pdbsum/5iyz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5iyz ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/TBA1B_BOVIN TBA1B_BOVIN]] 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. [[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/TBB2B_BOVIN TBB2B_BOVIN]] 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).
+[https://www.uniprot.org/uniprot/STMN4_RAT STMN4_RAT] Exhibits microtubule-destabilizing activity.<ref>PMID:15039434</ref> <ref>PMID:12111843</ref> <ref>PMID:15014504</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 5iyz" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Stathmin-4 3D structures|Stathmin-4 3D structures]]
+*[[Tubulin 3D Structures|Tubulin 3D Structures]]
+*[[Tubulin tyrosine ligase|Tubulin tyrosine ligase]]
 == References ==
 <references/>
@@ Line 23: / Line 29: @@
 </StructureSection>
 [[Category: Bos taurus]]
-[[Category: Bargsten, K]]
+[[Category: Gallus gallus]]
-[[Category: Doronina, S]]
+[[Category: Large Structures]]
-[[Category: Prota, A E]]
+[[Category: Rattus norvegicus]]
-[[Category: Steinmetz, M O]]
+[[Category: Bargsten K]]
-[[Category: Sussman, D]]
+[[Category: Doronina S]]
-[[Category: Waight, A B]]
+[[Category: Prota AE]]
-[[Category: Cell cycle]]
+[[Category: Steinmetz MO]]
-[[Category: Cytoskeleton]]
+[[Category: Sussman D]]
-[[Category: Microtubule]]
+[[Category: Waight AB]]
-[[Category: Tubulin fold]]

5iyz

From Proteopedia

Current revision

Tubulin-MMAE complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox