Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Design of proteasome inhibitors with oral efficacy in vivo against and selectivity over the human proteasome.
Journal, issue, pages	Proc Natl Acad Sci U S A, Vol. 118, Issue 39, Year 2021
Publish date	Sep 28, 2021
Authors	Stanley C Xie / Riley D Metcalfe / Hirotake Mizutani / Tanya Puhalovich / Eric Hanssen / Craig J Morton / Yawei Du / Con Dogovski / Shih-Chung Huang / Jeffrey Ciavarri / Paul Hales / Robert J Griffin / Lawrence H Cohen / Bei-Ching Chuang / Sergio Wittlin / Ioanna Deni / Tomas Yeo / Kurt E Ward / Daniel C Barry / Boyin Liu / David L Gillett / Benigno F Crespo-Fernandez / Sabine Ottilie / Nimisha Mittal / Alisje Churchyard / Daniel Ferguson / Anna Caroline C Aguiar / Rafael V C Guido / Jake Baum / Kirsten K Hanson / Elizabeth A Winzeler / Francisco-Javier Gamo / David A Fidock / Delphine Baud / Michael W Parker / Stephen Brand / Lawrence R Dick / Michael D W Griffin / Alexandra E Gould / Leann Tilley /
PubMed Abstract	The proteasome is a potential antimalarial drug target. We have identified a series of amino-amide boronates that are potent and specific inhibitors of the 20S proteasome (20S) β5 active site and ...The proteasome is a potential antimalarial drug target. We have identified a series of amino-amide boronates that are potent and specific inhibitors of the 20S proteasome (20S) β5 active site and that exhibit fast-acting antimalarial activity. They selectively inhibit the growth of compared with a human cell line and exhibit high potency against field isolates of and They have a low propensity for development of resistance and possess liver stage and transmission-blocking activity. Exemplar compounds, MPI-5 and MPI-13, show potent activity against infections in a SCID mouse model with an oral dosing regimen that is well tolerated. We show that MPI-5 binds more strongly to 20S than to human constitutive 20S (20Sc). Comparison of the cryo-electron microscopy (EM) structures of 20S and 20Sc in complex with MPI-5 and 20S in complex with the clinically used anti-cancer agent, bortezomib, reveal differences in binding modes that help to explain the selectivity. Together, this work provides insights into the 20S proteasome in , underpinning the design of potent and selective antimalarial proteasome inhibitors.
External links	Proc Natl Acad Sci U S A / PubMed:34548400 / PubMed Central
Methods	EM (single particle)
Resolution	3.1 - 3.4 Å
Structure data	23574 7lxt EMDB-23574, PDB-7lxt: Structure of Plasmodium falciparum 20S proteasome with bound bortezomib Method: EM (single particle) / Resolution: 3.4 Å 23575 7lxu EMDB-23575, PDB-7lxu: Structure of Plasmodium falciparum 20S proteasome with bound MPI-5 Method: EM (single particle) / Resolution: 3.1 Å 23576 7lxv EMDB-23576, PDB-7lxv: Structure of human 20S proteasome with bound MPI-5 Method: EM (single particle) / Resolution: 3.4 Å
Chemicals	ChemComp-BO2: N-[(1R)-1-(DIHYDROXYBORYL)-3-METHYLBUTYL]-N-(PYRAZIN-2-YLCARBONYL)-L-PHENYLALANINAMIDE / medication, anticancerYM / Bortezomib ChemComp-YHD*: N-[(1R)-2-([1,1'-biphenyl]-4-yl)-1-boronoethyl]-1-methyl-L-prolinamide
Source	Plasmodium falciparum 3D7 (eukaryote) plasmodium falciparum (isolate 3d7) (eukaryote) plasmodium falciparum (malaria parasite P. falciparum) Human (human) homo sapiens (human)
Keywords	HYDROLASE / proteasome / plasmodium falciparum / malaria / drug / bortezomib