Molecular interactions at the colchicine binding site in tubulin: An X-ray crystallography perspective.
Molecular interactions at the colchicine binding site in tubulin: An X-ray crystallography perspective.
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微管蛋白中秋水仙碱结合位点的分子相互作用：X射线晶体学观点。
DOI：
10.1016/j.drudis.2021.12.001
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发表时间：
2022-03
影响因子：
7.4
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Wang J;Miller DD;Li W
微管蛋白是重要的癌症药物靶点。与微管蛋白中的秋水仙碱位点结合的化合物引起了人们的极大兴趣，因为与其他潜在药物相比，它们通常较少受到多药耐药性的影响。建模有助于理解微管蛋白和秋水仙碱结合位点抑制剂 (CBSI) 之间的相互作用，但由于秋水仙碱结合位点包含两个柔性环，其构象高度配体依赖性，因此建模有其局限性。 X 射线晶体学提供了这个具有挑战性的秋水仙碱位点的微管蛋白-配体相互作用的实验图片。自2004年第一个微管蛋白与N-脱乙酰基-N-(2-巯基乙酰基)-秋水仙碱复合物(DAMA-秋水仙碱)的X射线结构发表以来，许多涉及秋水仙碱结合位点的微管蛋白复合物的X射线晶体结构被报道。在这篇综述中，我们总结了微管蛋白与各种CBSI复合物的晶体结构，旨在促进新一代微管蛋白抑制剂的发现。在过去的十年中，X 射线晶体学极大地促进了利用秋水仙碱结合位点的新一代微管蛋白抑制剂的发现和开发。
Tubulin is an important cancer drug target. Compounds that bind at the colchicine site in tubulin have attracted significant interest as they are generally less affected by multidrug resistance than are other potential drugs. Modeling is useful in understanding the interactions between tubulin and colchicine binding site inhibitors (CBSIs), but because the colchicine binding site contains two flexible loops whose conformations are highly ligand-dependent, modeling has its limitations. X-ray crystallography provides experimental pictures of tubulin–ligand interactions at this challenging colchicine site. Since 2004, when the first X-ray structure of tubulin in complex with N-deacetyl-N-(2-mercaptoacetyl)-colchicine (DAMA-colchicine) was published, many X-ray crystal structures have been reported for tubulin complexes involving the colchicine binding site. In this review, we summarize the crystal structures of tubulin in complexes with various CBSIs, aiming to facilitate the discovery of new generations of tubulin inhibitors. Over the past decade, X-ray crystallography has greatly facilitated the discovery and development of new generations of tubulin inhibitors that utilize the colchicine binding site.
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影响因子：
7.3
作者：
Canela, Maria-Dolores;Perez-Perez, Maria-Jesus;Priego, Eva-Maria
通讯作者：
Priego, Eva-Maria
影响因子：
4.2
作者：
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作者：
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作者：
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通讯作者：
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影响因子：
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作者：
Chapman, Henry N.;Fromme, Petra;Barty, Anton;White, Thomas A.;Kirian, Richard A.;Aquila, Andrew;Hunter, Mark S.;Schulz, Joachim;DePonte, Daniel P.;Weierstall, Uwe;Doak, R. Bruce;Maia, Filipe R. N. C.;Martin, Andrew V.;Schlichting, Ilme;Lomb, Lukas;Coppola, Nicola;Shoeman, Robert L.;Epp, Sascha W.;Hartmann, Robert;Rolles, Daniel;Rudenko, Artem;Foucar, Lutz;Kimmel, Nils;Weidenspointner, Georg;Holl, Peter;Liang, Mengning;Barthelmess, Miriam;Caleman, Carl;Boutet, Sebastien;Bogan, Michael J.;Krzywinski, Jacek;Bostedt, Christoph;Bajt, Sasa;Gumprecht, Lars;Rudek, Benedikt;Erk, Benjamin;Schmidt, Carlo;Hoemke, Andre;Reich, Christian;Pietschner, Daniel;Strueder, Lothar;Hauser, Guenter;Gorke, Hubert;Ullrich, Joachim;Herrmann, Sven;Schaller, Gerhard;Schopper, Florian;Soltau, Heike;Kuehnel, Kai-Uwe;Messerschmidt, Marc;Bozek, John D.;Hau-Riege, Stefan P.;Frank, Matthias;Hampton, Christina Y.;Sierra, Raymond G.;Starodub, Dmitri;Williams, Garth J.;Hajdu, Janos;Timneanu, Nicusor;Seibert, M. Marvin;Andreasson, Jakob;Rocker, Andrea;Joensson, Olof;Svenda, Martin;Stern, Stephan;Nass, Karol;Andritschke, Robert;Schroeter, Claus-Dieter;Krasniqi, Faton;Bott, Mario;Schmidt, Kevin E.;Wang, Xiaoyu;Grotjohann, Ingo;Holton, James M.;Barends, Thomas R. M.;Neutze, Richard;Marchesini, Stefano;Fromme, Raimund;Schorb, Sebastian;Rupp, Daniela;Adolph, Marcus;Gorkhover, Tais;Andersson, Inger;Hirsemann, Helmut;Potdevin, Guillaume;Graafsma, Heinz;Nilsson, Bjoern;Spence, John C. H.
通讯作者：
Spence, John C. H.