T. brucei Phosphodiesterase B1

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T. brucei Phosphodiesterase B1

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Contents 1 Function 2 Relevance 3 Structural highlights 4 Citations

Function

3′,5′-cyclic nucleotide phosphodiesterases (PDEs) are enzymes that hydrolyse 3',5'-phosphodiester bonds in two of the most important cell signalling molecules, cyclic-adenosine monophosphates (cAMPs) and cyclic-guanosine monophosphates (cGMPs). PDEs are essential for the inactivation of cAMP and or cGMP to regulate their intracellular concentrations and maintain cellular homeostasis ^[1]. PDEs directly modulate these messenger molecules by degrading cAMP or cGMP when concentrations are elevated beyond the cellular threshold ^[2]. is one of two cyclic nucleotide phosphodiesterases that have been validated as promising drug targets for the treatment of human African trypanosomiasis, also known as sleeping sickness ^[3].

Relevance

Structural highlights

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Citations

1. ↑ Baker DA. Cyclic nucleotide signalling in malaria parasites. Cell Microbiol. 2011 Mar;13(3):331-9. doi: 10.1111/j.1462-5822.2010.01561.x. Epub, 2010 Dec 28. PMID:21176056 doi:http://dx.doi.org/10.1111/j.1462-5822.2010.01561.x
2. ↑ Blaazer AR, Singh AK, de Heuvel E, Edink E, Orrling KM, Veerman JJN, van den Bergh T, Jansen C, Balasubramaniam E, Mooij WJ, Custers H, Sijm M, Tagoe DNA, Kalejaiye TD, Munday JC, Tenor H, Matheeussen A, Wijtmans M, Siderius M, de Graaf C, Maes L, de Koning HP, Bailey DS, Sterk GJ, de Esch IJP, Brown DG, Leurs R. Targeting a Subpocket in Trypanosoma brucei Phosphodiesterase B1 (TbrPDEB1) Enables the Structure-Based Discovery of Selective Inhibitors with Trypanocidal Activity. J Med Chem. 2018 May 1. doi: 10.1021/acs.jmedchem.7b01670. PMID:29672041 doi:http://dx.doi.org/10.1021/acs.jmedchem.7b01670
3. ↑ Jansen C, Wang H, Kooistra AJ, de Graaf C, Orrling KM, Tenor H, Seebeck T, Bailey D, de Esch IJ, Ke H, Leurs R. Discovery of Novel Trypanosoma brucei Phosphodiesterase B1 Inhibitors by Virtual Screening against the Unliganded TbrPDEB1 Crystal Structure. J Med Chem. 2013 Mar 1. PMID:23409953 doi:http://dx.doi.org/10.1021/jm3017877