Binding mode of TMC-95A analogues to eukaryotic 20S proteasome

Chembiochem : a European Journal of Chemical Biology
Markus KaiserLuis Moroder

Abstract

The complex thermodynamics that govern noncovalent protein-ligand interactions are still not fully understood, despite the exponential increase in experimental structural data available from X-ray crystallography and NMR spectroscopy. The eukaryotic 20S proteasome offers an ideal system for such studies as it contains in duplicate three proteolytically active sites with different substrate specificities. The natural product TMC-95A inhibits these proteolytic centers noncovalently with distinct affinities. X-ray crystallographic analysis of the complexes of the yeast proteasome core particle with this natural inhibitor and two synthetic analogues clearly revealed highly homologous hydrogen-bonding networks involving mainly the peptide backbone despite the strongly differentiated binding affinities to the three active sites of the 20S proteasome. The natural product and the two analogues are constrained in a rigid beta-type extended conformation by the endocyclic biaryl clamp, which preorganizes the peptide backbone for optimal adaptation of the ligands to the active site clefts and thus favors the binding processes entropically. However, the biaryl clamp also dictates the orientation of the P1 and P3 residues and their mode of i...Continue Reading

References

Dec 5, 1987·Journal of Molecular Biology·A WlodawerC Woodward
Dec 16, 1983·Biochemical and Biophysical Research Communications·M RanceK Wüthrich
Dec 15, 1996·Acta Crystallographica. Section C, Crystal Structure Communications·J W JanetkaD H Rich
Oct 6, 1997·The Journal of Biological Chemistry·W HeinemeyerD H Wolf
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Oct 6, 1998·Annual Review of Biochemistry·A Hershko, A Ciechanover
Oct 15, 1998·Proceedings of the National Academy of Sciences of the United States of America·A K NussbaumH Schild
Jun 8, 1999·Annual Review of Immunology·K L Rock, A L Goldberg
Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·M GrollR Huber
Apr 12, 2000·Journal of Peptide Science : an Official Publication of the European Peptide Society·G LoidlL Moroder
May 18, 2000·The Journal of Organic Chemistry·J KohnoS Komatsubara
Nov 4, 2000·Nature Structural Biology·M GrollD Finley
Nov 30, 2000·Archives of Biochemistry and Biophysics·M Orlowski, S Wilk
Jun 8, 2001·Bioorganic & Medicinal Chemistry Letters·C García-EcheverríaP Furet
Jun 19, 2001·Medicinal Research Reviews·J MyungC M Crews
Aug 22, 2001·Chemistry & Biology·A F Kisselev, A L Goldberg
Apr 3, 2002·Trends in Molecular Medicine·Julian Adams
Apr 3, 2002·Nature Medicine·Alfred L Goldberg, Kenneth Rock
May 17, 2002·Structure·Masaki UnnoTomitake Tsukihara
Dec 20, 2002·Angewandte Chemie·Markus KaiserLuis Moroder
Jan 17, 2003·Organic Letters·Brian K Albrecht, Robert M Williams
Mar 5, 2003·Journal of Molecular Biology·Michael GrollRobert Huber
Jun 10, 2003·Chembiochem : a European Journal of Chemical Biology·Zhi-Qiang YangSamuel J Danishefsky
Jun 19, 2003·Angewandte Chemie·Masayuki InoueMasahiro Hirama
Dec 17, 2003·Current Opinion in Structural Biology·Michael Groll, Tim Clausen
Dec 29, 2006·Chemistry & Biodiversity·Markus KaiserLuis Moroder

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Citations

Apr 4, 2013·Journal of Medicinal Chemistry·Sevil OzcanSaïd M Sebti
Apr 11, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jérôme ClercMarkus Kaiser
Feb 25, 2014·Organic Letters·Alexis CosteGwilherm Evano
Sep 20, 2007·Organic & Biomolecular Chemistry·Nityakalyani SrinivasJohn A Robinson
Sep 10, 2011·Natural Product Reports·Daniel KrahnMarkus Kaiser
Mar 24, 2012·European Journal of Medicinal Chemistry·Xavier MaréchalJoëlle Vidal
Jan 8, 2016·Annual Review of Pharmacology and Toxicology·Paweł Śledź, Wolfgang Baumeister
Jan 29, 2005·Chembiochem : a European Journal of Chemical Biology·Michael GrollRobert Huber
Sep 12, 2009·Chembiochem : a European Journal of Chemical Biology·Jérôme ClercMarkus Kaiser
Mar 26, 2013·Angewandte Chemie·Andreas RentschMarkus Kalesse
Sep 4, 2010·Journal of Peptide Science : an Official Publication of the European Peptide Society·Anna BaldisserottoRoberto Tomatis
Mar 4, 2014·Medicinal Research Reviews·Nicola MicaleMaria Zappalà
Jul 10, 2010·Biochimie·Geoffroy de Bettignies, Olivier Coux
Jan 31, 2013·Biochimica Et Biophysica Acta·Martin L Stein, Michael Groll
Jan 26, 2008·Organic & Biomolecular Chemistry·Mathieu Pucheault
Nov 1, 2011·Chemical Communications : Chem Comm·Melissa Ann Gräwert, Michael Groll
Oct 30, 2013·Dalton Transactions : an International Journal of Inorganic Chemistry·Emilia FuriaGiovanni Sindona
Mar 5, 2019·ChemMedChem·Roberta EttariMaria Zappalà
Feb 20, 2020·Acta Crystallographica. Section E, Crystallographic Communications·Thuy Quynh LeThai Thanh Thu Bui
Oct 30, 2020·Acta Crystallographica. Section E, Crystallographic Communications·Xuan Tu NguyenThai Thanh Thu Bui
Feb 24, 2007·Chemical Reviews·Ljudmila Borissenko, Michael Groll
May 9, 2014·The Journal of Organic Chemistry·Carlo SicilianoAndrea Temperini
Oct 27, 2018·Journal of Medicinal Chemistry·Sanil BhatiaFinn K Hansen
May 22, 2007·Journal of Medicinal Chemistry·Nicolas BasseJoëlle Vidal

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