Inhibition mechanism of SAHA in HDAC: a revisit
Literature Information
Jingwei Zhou, Ruibo Wu
SAHA (vorinostat, Merck) is a famous clinical drug for zinc-containing histone deacetylase (HDAC) targets against cancer and several other human disorders, whose inhibition mechanism (namely the protonation mechanism) upon binding to HDAC has been debated for more than ten years. It is very challenging to verify experimentally and is still controversial theoretically. The popular “Class-dependent” (namely “Tyr-dependent”) hypothesis is that the deprotonation of SAHA is mostly regulated by the conserved Tyr308 in class I HDAC while it is replaced by the His843 in class IIa HDAC. Herein, by elaborate QM(DFT)/MM MD simulations, we exclude the prevalent “Class-dependent” mechanism and advance a novel “Metal-dependent” mechanism, where the remote second metal site (K+ in most HDAC and Ca2+ in HDAC2) determines the protonation of SAHA. This proof-of-principle “Metal-dependent” mechanism opens up a new avenue to utilize the second metal site for isoform-selective inhibitor design.
Related Literature
Bis(N-acylated imidazolin-2-imine) nickel catalyzed norbornene copolymerization with methyl acrylate
Hu Zhang, Ru Xiao, Zhengguo Cai
DOI: 10.1039/D0PY00857E
Semiaromatic polyamides with enhanced charge carrier mobility
Bilal Özen, Nicolas Candau, Cansel Temiz, Ferdinand C. Grozema, Grégory Stoclet, Christopher J. G. Plummer, Holger Frauenrath
DOI: 10.1039/D1PY01203G
Sustainable synthesis of CO2-derived polycarbonates from d-xylose
David K. Tran, Ahmed Z. Rashad, Donald J. Darensbourg
DOI: 10.1039/D1PY00784J
Imidazole based dual photo/thermal initiators for highly efficient radical polymerization under air with a metal-free approach‡
DOI: 10.1039/D1PY01079D
Tunable hydantoin and base binary organocatalysts in ring-opening polymerizations
Lei Zhang, Fangyuan Zhou, Zhenjiang Li, Bo Liu, Rui Yan, Jie Li, Yongzhu Hu, Chan Zhang, Zikun Luo, Kai Guo
DOI: 10.1039/D0PY00812E
The influences of monomer structure and solvent on the radical copolymerization of tertiary amine and PEGylated methacrylates
Priscila Quiñonez-Angulo, Robin A. Hutchinson, Ángel Licea-Claveríe, Enrique Saldívar-Guerra, Iván Zapata-González
DOI: 10.1039/D1PY00750E
Aqueous copper-mediated reversible deactivation radical polymerization (RDRP) utilizing polyetheramine derived initiators‡
Jirui Zhang, Evelina Liarou, James Town, Yongguang Li, Alan M. Wemyss, David M. Haddleton
DOI: 10.1039/D0PY00555J
Role of thiol oxidation by air in the mechanism of the self-initiated thermal thiol–ene polymerization
DOI: 10.1039/D1PY01301G
Thermoresponsive polymers as macromolecular coordination ligands: complexation-dependence of thermally induced aggregation in aqueous solution
Maximilian Felix Toni Meier, Franck Thetiot, Narsimhulu Pittala, Ingo Lieberwirth, Cleiton Kunzler, Smail Triki, Ulrich Jonas
DOI: 10.1039/D1PY00847A
Aluminum-catalyzed statistical copolymerization of mono-, tri- and penta-fluorophenyl glycidyl ether with ethylene oxide and epichlorohydrin
Fang Guo, Ming Deng, Fan Li, Shoulong Chen
DOI: 10.1039/D1PY00938A
You might also like
What is the market or research trend for N-(4-Methoxybenzyl)-2-pyridinamine (CAS: 52818-63-0)?
N-(4-Methoxybenzyl)-2-pyridinamine (CAS: 52818-63-0) is increasingly being used ...
What precautions should be taken when handling Ethyl 4-(2-chlorophenyl)-1,3-thiazole-2-carboxylate (CAS: 1050507-06-6)?
When handling Ethyl 4-(2-chlorophenyl)-1,3-thiazole-2-carboxylate, appropriate p...
What regulatory guidelines apply to diethyldiselane (CAS: 628-39-7)?
Diethyldiselane (CAS: 628-39-7) is classified under the Globally Harmonized Syst...
What is the market or research trend for oxocopper (CAS: 12053-18-8)?
The market for oxocopper (CAS: 12053-18-8) is primarily driven by its use in cat...
What is the market or research trend for 5-{[(2-Methyl-2-propanyl)oxy]carbonyl}-5-azaspiro[2.4]heptane-7-carboxylic acid?
The market for 5-{[(2-Methyl-2-propanyl)oxy]carbonyl}-5-azaspiro[2.4]heptane-7-c...
What is 2-(1-Pyrrolidinyl)-4-pyridinamine (CAS: 35981-63-6)?
2-(1-Pyrrolidinyl)-4-pyridinamine is a chemical compound with the CAS number 359...
What are the physical and chemical properties of 2-(3-Pyridinyl)-1-azabicyclo[2.2.2]octane (CAS: 91556-75-1)?
2-(3-Pyridinyl)-1-azabicyclo[2.2.2]octane (CAS: 91556-75-1) is a crystalline sol...
How is (S)-Alpha-allyl-proline hydrochloride (CAS: 129704-91-2) typically synthesized?
(S)-Alpha-allyl-proline hydrochloride is usually synthesized via a Wittig reacti...
What is 3-Methyl-1,2-oxazole-5-carboxylic acid (CAS: 4857-42-5)?
3-Methyl-1,2-oxazole-5-carboxylic acid (CAS: 4857-42-5) is an organic compound w...
How is Lys-SMCC-DM1 (CAS: 1281816-04-3) typically synthesized?
Lys-SMCC-DM1 is synthesized via a multi-step process involving the coupling of S...
Source Journal
Physical Chemistry Chemical Physics

Physical Chemistry Chemical Physics (PCCP) is an international journal co-owned by 19 physical chemistry and physics societies from around the world. This journal publishes original, cutting-edge research in physical chemistry, chemical physics and biophysical chemistry. To be suitable for publication in PCCP, articles must include significant innovation and/or insight into physical chemistry; this is the most important criterion that reviewers and Editors will judge against when evaluating submissions. The journal has a broad scope and welcomes contributions spanning experiment, theory, computation and data science. Topical coverage includes spectroscopy, dynamics, kinetics, statistical mechanics, thermodynamics, electrochemistry, catalysis, surface science, quantum mechanics, quantum computing and machine learning. Interdisciplinary research areas such as polymers and soft matter, materials, nanoscience, energy, surfaces/interfaces, and biophysical chemistry are welcomed if they demonstrate significant innovation and/or insight into physical chemistry. Joined experimental/theoretical studies are particularly appreciated when complementary and based on up-to-date approaches.













![1,10-bis(3,5-dimethylphenyl)-12-hydroxy-4,5,6,7-tetrahydroiindeno[7,1-de:1',7'-fg][1,3,2]dioxaphosphocine 12-oxide structure 1,10-bis(3,5-dimethylphenyl)-12-hydroxy-4,5,6,7-tetrahydroiindeno[7,1-de:1',7'-fg][1,3,2]dioxaphosphocine 12-oxide structure](https://static.chemtradehub.com/structs/141/1412439-82-7-b9a9.webp)
