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@article{1410057, author = {Marques, Sérgio Manuel and Daniel, Lukáš and Buryška, Tomáš and Prokop, Zbyněk and Brezovský, Jan and Damborský, Jiří}, article_location = {Hoboken, USA}, article_number = {5}, doi = {http://dx.doi.org/10.1002/med.21430}, keywords = {drug design; protein tunnels; protein gates; drug binding; selectivity; specificity}, language = {eng}, issn = {0198-6325}, journal = {MEDICINAL RESEARCH REVIEWS}, title = {Enzyme Tunnels and Gates As Relevant Targets in Drug Design}, url = {https://loschmidt.chemi.muni.cz/peg/wp-content/uploads/2016/12/Marques_16res_rev.pdf}, volume = {37}, year = {2017} }
TY - JOUR ID - 1410057 AU - Marques, Sérgio Manuel - Daniel, Lukáš - Buryška, Tomáš - Prokop, Zbyněk - Brezovský, Jan - Damborský, Jiří PY - 2017 TI - Enzyme Tunnels and Gates As Relevant Targets in Drug Design JF - MEDICINAL RESEARCH REVIEWS VL - 37 IS - 5 SP - 1095-1139 EP - 1095-1139 PB - WILEY SN - 01986325 KW - drug design KW - protein tunnels KW - protein gates KW - drug binding KW - selectivity KW - specificity UR - https://loschmidt.chemi.muni.cz/peg/wp-content/uploads/2016/12/Marques_16res_rev.pdf N2 - Many enzymes contain tunnels and gates that are essential to their function. Gates reversibly switch between open and closed conformations and thereby control the traffic of small molecules-substrates, products, ions, and solvent molecules-into and out of the enzyme's structure via molecular tunnels. Many transient tunnels and gates undoubtedly remain to be identified, and their functional roles and utility as potential drug targets have received comparatively little attention. Here, we describe a set of general concepts relating to the structural properties, function, and classification of these interesting structural features. In addition, we highlight the potential of enzyme tunnels and gates as targets for the binding of small molecules. The different types of binding that are possible and the potential pharmacological benefits of such targeting are discussed. Twelve examples of ligands bound to the tunnels and/or gates of clinically relevant enzymes are used to illustrate the different binding modes and to explain some new strategies for drug design. Such strategies could potentially help to overcome some of the problems facing medicinal chemists and lead to the discovery of more effective drugs. ER -
MARQUES, Sérgio Manuel, Lukáš DANIEL, Tomáš BURYŠKA, Zbyněk PROKOP, Jan BREZOVSKÝ and Jiří DAMBORSKÝ. Enzyme Tunnels and Gates As Relevant Targets in Drug Design. \textit{MEDICINAL RESEARCH REVIEWS}. Hoboken, USA: WILEY, 2017, vol.~37, No~5, p.~1095-1139. ISSN~0198-6325. Available from: https://dx.doi.org/10.1002/med.21430.
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