ArticleMolecular microbiology2007
Crystal structure of the Leishmania major phosphodiesterase LmjPDEB1 and insight into the design of the parasite-selective inhibitors.
Article in Molecular microbiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 63 citations in OpenAlex.
- Discovery of 5-Phenylpyrazolopyrimidinone Analogs as Potent Antitrypanosomal Agents with In Vivo Efficacy.Journal of medicinal chemistry · 2023Article
- To Target or Not to TargetInternational journal of molecular sciences · 2023Article
- In Vitro, In Vivo and In Silico Effectiveness of LASSBio-1386, anFrontiers in pharmacology · 2020Article
- Evaluation of Modulators of cAMP-Response in Terms of Their Impact on Cell Cycle and Mitochondrial Activity ofFrontiers in pharmacology · 2020Article
- Methods to Investigate Signal Transduction Pathways in Trypanosoma cruzi: Cyclic Nucleotide Phosphodiesterases Assay Protocols.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Cyclic Nucleotide-Specific Phosphodiesterases as Potential Drug Targets for Anti-Leishmania Therapy.Antimicrobial agents and chemotherapy · 2018Article
- Targeting a Subpocket in Trypanosoma brucei Phosphodiesterase B1 (TbrPDEB1) Enables the Structure-Based Discovery of Selective Inhibitors with Trypanocidal Activity.Journal of medicinal chemistry · 2018Article
- The single cyclic nucleotide-specific phosphodiesterase of the intestinal parasite Giardia lamblia represents a potential drug target.PLoS neglected tropical diseases · 2017Article
- The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases-Part III: In-Silico Molecular Docking Investigations.Molecules (Basel, Switzerland) · 2016Review
- Crystal structure of the Legionella pneumophila Lem10 effector reveals a new member of the HD protein superfamily.Proteins · 2015Article
- Structural Asymmetry of Phosphodiesterase-9A and a Unique Pocket for Selective Binding of a Potent Enantiomeric Inhibitor.Molecular pharmacology · 2015Article
- Structure of the Legionella Effector, lpg1496, Suggests a Role in Nucleotide Metabolism.The Journal of biological chemistry · 2015Article
- cAMP signalling in trypanosomatids: role in pathogenesis and as a drug target.Trends in parasitology · 2015Review
- The ever unfolding story of cAMP signaling in trypanosomatids: vive la difference!Frontiers in pharmacology · 2015Review
- Recent developments in drug discovery for leishmaniasis and human African trypanosomiasis.Chemical reviews · 2014Review
- Transcriptome sequencing and analysis of the zoonotic parasite Spirometra erinacei spargana (plerocercoids).Parasites & vectors · 2014Article
- Synthesis and assessment of catechol diether compounds as inhibitors of trypanosomal phosphodiesterase B1 (TbrPDEB1).Bioorganic & medicinal chemistry letters · 2013Article
- In-silico Leishmania target selectivity of antiparasitic terpenoids.Molecules (Basel, Switzerland) · 2013Article
- Discovery of novel Trypanosoma brucei phosphodiesterase B1 inhibitors by virtual screening against the unliganded TbrPDEB1 crystal structure.Journal of medicinal chemistry · 2013Article
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6 authors at 2 institutions in 2 countries.
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Abstract
Human leishmaniasis is a major public health problem in many countries, but chemotherapy is in an unsatisfactory state. Leishmania major phosphodiesterases (LmjPDEs) have been shown to play important roles in cell proliferation and apoptosis of the parasite. Thus LmjPDE inhibitors may potentially represent a novel class of drugs for the treatment of leishmaniasis. Reported here are the kinetic characterization of the LmjPDEB1 catalytic domain and its crystal structure as a complex with 3-isobutyl-1-methylxanthine (IBMX) at 1.55 A resolution. The structure of LmjPDEB1 is similar to that of human PDEs. IBMX stacks against the conserved phenylalanine and forms a hydrogen bond with the invariant glutamine, in a pattern common to most inhibitors bound to human PDEs. However, an extensive structural comparison reveals subtle, but significant differences between the active sites of LmjPDEB1 and human PDEs. In addition, a pocket next to the inhibitor binding site is found to be unique to LmjPDEB1. This pocket is isolated by two gating residues in human PDE families, but constitutes a natural expansion of the inhibitor binding pocket in LmjPDEB1. The structure particularity might be useful for the development of parasite-selective inhibitors for the treatment of leishmaniasis.
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