Sekikaic acid and lobaric acid target a dynamic interface of the coactivator CBP/p300.
Sekikaic acid and lobaric acid target a dynamic interface of the coactivator CBP/p300.
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DOI：
10.1002/anie.201206815
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发表时间：
2012-11-05
期刊：
影响因子：
--
通讯作者：
Mapp AK
中科院分区：
文献类型：
--
作者：
Majmudar CY;Højfeldt JW;Arevang CJ;Pomerantz WC;Gagnon JK;Schultz PJ;Cesa LC;Doss CH;Rowe SP;Vásquez V;Tamayo-Castillo G;Cierpicki T;Brooks CL 3rd;Sherman DH;Mapp AK
Although there have been recent notable successes in the discovery of ligands that target stable, high-affinity protein–protein interactions (PPIs), the transient and moderate affinity PPIs that underpin many fundamental cellular processes have proven to be far less tractable for ligand discovery.[1] Prime examples of this are the dynamic complexes formed between DNA-bound transcriptional activators and coactivators that are part of eukaryotic transcription initiation.[1b, 2] In this instance, complex formation is mediated through interactions that are transient and only of moderate affinity (KDs of 0.1–10 μm).[3] An additional complication common to transient/modest affinity PPIs is that one or both of the binding interfaces is often used for complex formation with a variety of partners (Figure 1a).[4] Specificity is often fine-tuned in these complexes by allosteric regulation, with the binding of one ligand influencing the affinity of another ligand (Figure 1 b).[5] Small molecules that can take advantage of these dynamic binding interfaces could potentially modulate the binding of ligands at multiple different sites on a protein yet maintain specificity for the target protein.[6] Herein we report the identification of two uniquely specific ligands for the coactivator CBP/p300 that are of the depside (sekikaic acid) and depsidone (lobaric acid) natural product family, a group first identified by Emil Fischer in the early 20th century as polypeptide-like small molecules consisting of a series of phenol carboxylic acids units.[7] Through interaction with a dynamic surface of the CBP/p300 GACKIX domain, these molecules effectively inhibit the ability of two
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影响因子：
3.5
作者：
Arai M;Dyson HJ;Wright PE
通讯作者：
Wright PE
影响因子：
4
作者：
Buhrlage, Sara J.;Bates, Caleb A.;Rowe, Steven P.;Minter, Aaron R.;Brennan, Brian B.;Majmudar, Chinmay Y.;Wemmer, David E.;Al-Hashimi, Hashim;Mapp, Anna K.
通讯作者：
Mapp, Anna K.
影响因子：
4.8
作者：
Hermann, S;Berndt, KD;Wright, AP
通讯作者：
Wright, AP
影响因子：
5.6
作者：
De Guzman, RN;Goto, NK;Wright, PE
通讯作者：
Wright, PE
DOI：
10.1073/pnas.95.23.13543
发表时间：
1998-11-10
影响因子：
11.1
作者：
Ansari, AZ;Reece, RJ;Ptashne, M
通讯作者：
Ptashne, M