Plasmodium falciparum proteasome subunit beta type-5 | Antimalarial targets | IUPHAR/MMV Guide to MALARIA PHARMACOLOGY

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Plasmodium falciparum proteasome subunit beta type-5

Target id: 3088

Nomenclature: Plasmodium falciparum proteasome subunit beta type-5

Family: Antimalarial targets

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Plasmodium falciparum 3D7 - 271 PF3D7_1011400 proteasome subunit beta type-5
Database Links
PlasmoDB
UniProtKB
Malaria Pharmacology Comments
The eukaryotic 26S proteasome is a multi-subunit protease complex that is involved in diverse cellular processes. It consists of a 20S catalytic core capped at one or both ends by 19S regulatory complexes, with a recent study elucidating the structure of the P. falciparum 20S core (PDB ID: 5FMG,[4]). Proteasome inhibitors have been shown to have potential as antimalarial therapies that are effective against multiple stages of the P. falciparum lifecycle [1-2], but have been precluded from clinical development because of low species selectivity. Next-generation proteasome inhibitors that target the Β2 and Β5 subunits of the P. falciparum 20S core have been developed and these exhibit improved selectivity for the malaria parasite [3-5].

References

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1. Czesny B, Goshu S, Cook JL, Williamson KC. (2009) The proteasome inhibitor epoxomicin has potent Plasmodium falciparum gametocytocidal activity. Antimicrob. Agents Chemother., 53 (10): 4080-5. [PMID:19651911]

2. Gantt SM, Myung JM, Briones MR, Li WD, Corey EJ, Omura S, Nussenzweig V, Sinnis P. (1998) Proteasome inhibitors block development of Plasmodium spp. Antimicrob. Agents Chemother., 42 (10): 2731-8. [PMID:9756786]

3. Kirkman LA, Zhan W, Visone J, Dziedziech A, Singh PK, Fan H, Tong X, Bruzual I, Hara R, Kawasaki M et al.. (2018) Antimalarial proteasome inhibitor reveals collateral sensitivity from intersubunit interactions and fitness cost of resistance. Proc. Natl. Acad. Sci. U.S.A., 115 (29): E6863-E6870. [PMID:29967165]

4. Li H, O'Donoghue AJ, van der Linden WA, Xie SC, Yoo E, Foe IT, Tilley L, Craik CS, da Fonseca PC, Bogyo M. (2016) Structure- and function-based design of Plasmodium-selective proteasome inhibitors. Nature, 530 (7589): 233-6. [PMID:26863983]

5. Stokes BH, Yoo E, Murithi JM, Luth MR, Afanasyev P, da Fonseca PCA, Winzeler EA, Ng CL, Bogyo M, Fidock DA. (2019) Covalent Plasmodium falciparum-selective proteasome inhibitors exhibit a low propensity for generating resistance in vitro and synergize with multiple antimalarial agents. PLoS Pathog., 15 (6): e1007722. [PMID:31170268]

How to cite this page

Antimalarial targets: Plasmodium falciparum proteasome subunit beta type-5. Last modified on 16/09/2019. Accessed on 19/11/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3088.