Towards the mechanism of trimeric purine nucleoside phosphorylases: Stopped-flow studies of binding of multisubstrate analogue inhibitor — 2-amino-9-[2-(phosphonomethoxy)ethyl]-6-sulfanylpurine

Wielgus‐Kutrowska, Beata; Antosiewicz, Jan; Długosz, Maciej; Holý, Antonı́n; Bzowska, Agnieszka

doi:10.1016/j.bpc.2006.08.008

Cited by 10 publications

(15 citation statements)

References 34 publications

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“…Wielgus-Kutrowska et al . [150] studied the binding of 2-amino-9-[2-(phosphonome-thoxy) ethyl]-6-sulfanylpurine (PME-6-thio-Gua) to PNP from Cellulomanoas sp. They determined that the binding of the ligand to PNP is a one-step process.…”

Section: Application Domainsmentioning

confidence: 99%

Computational Methods for De novo Protein Design and its Applications to the Human Immunodeficiency Virus 1, Purine Nucleoside Phosphorylase, Ubiquitin Specific Protease 7, and Histone Demethylases

Bellows¹,

Floudas²

2010

CDT

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This paper provides an overview of computational de novo protein design methods, highlighting recent advances and successes. Four protein systems are described that are important targets for drug design: human immunodeficiency virus 1, purine nucleoside phosphorylase, ubiquitin specific protease 7, and histone demethylases. Target areas for drug design for each protein are described, along with known inhibitors, focusing on peptidic inhibitors, but also describing some smallmolecule inhibitors. Computational design methods that have been employed in elucidating these inhibitors for each protein are outlined, along with steps that can be taken in order to apply computational protein design to a system that has mainly used experimental methods to date. KeywordsComputational protein design; human immunodeficiency virus 1; purine nucleoside phosphorylase; ubiquitin specific protease 7; histone demethylases

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Section: Application Domainsmentioning

confidence: 99%

Computational Methods for De novo Protein Design and its Applications to the Human Immunodeficiency Virus 1, Purine Nucleoside Phosphorylase, Ubiquitin Specific Protease 7, and Histone Demethylases

Bellows¹,

Floudas²

2010

CDT

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“…Inhibitors of human and parasitic PNPase are considered potential immunodepressive and anti-parasitic agents 94 . They may also have utility in the treatment of human T-cell leukemia, autoimmune disorders, and in the prevention of transplant rejection 95,96 .…”

Section: Purine Nucleoside Phosphorylasementioning

confidence: 99%

“…Two new potent inhibitors 37b, n = 5 and n = 6, which were stable mimics of 37a, were identified. They had K i (inosine as variable substrate) in the nanomolar range when assayed in the presence of zinc chloride 94 . From this study, a model assuming interacting binding sites was more probable than the hypothesized dependent sites model.…”

Section: Purine Nucleoside Phosphorylasementioning

confidence: 99%

Multisubstrate adduct inhibitors: Drug design and biological tools

Calvez

Scott²,

Migaud

2009

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…PNP inhibitors are used to reduce the immune response in the transplantation of organs and tissues or during chemotherapy (Morris et al, 2000;Farutin et al, 1999). Therefore, PNPs remain attractive targets for inhibitor development (Wielgus-Kutrowska et al, 2007). Potent inhibitors of PNP are frequently structural analogues of nucleoside substrates that have been modified in the base or pentose component (Wielgus-Kutrowska et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, PNPs remain attractive targets for inhibitor development (Wielgus-Kutrowska et al, 2007). Potent inhibitors of PNP are frequently structural analogues of nucleoside substrates that have been modified in the base or pentose component (Wielgus-Kutrowska et al, 2007). One of these inhibitors that can be used as a lead compound for structurebased drug design is acyclovir [9-(2 0 -hydroxyethoxymethyl)- guanine; ACV].…”

Section: Introductionmentioning

confidence: 99%

Crystal structure ofEscherichia colipurine nucleoside phosphorylase complexed with acyclovir

et al. 2018

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Escherichia coli purine nucleoside phosphorylase (PNP), which catalyzes the reversible phosphorolysis of purine ribonucleosides, belongs to the family I hexameric PNPs. Owing to their key role in the purine salvage pathway, PNPs are attractive targets for drug design against some pathogens. Acyclovir (ACV) is an acyclic derivative of the PNP substrate guanosine and is used as an antiviral drug for the treatment of some human viral infections. The crystalline complex of E. coli PNP with acyclovir was prepared by co-crystallization in microgravity using counter-diffusion through a gel layer in a capillary. The structure of the E. coli PNP-ACV complex was solved at 2.32 Å resolution using the molecular-replacement method. The ACV molecule is observed in two conformations and sulfate ions were located in both the nucleoside-binding and phosphate-binding pockets of the enzyme. A comparison with the complexes of other hexameric and trimeric PNPs with ACV shows the similarity in acyclovir binding by these enzymes.

show abstract

Towards the mechanism of trimeric purine nucleoside phosphorylases: Stopped-flow studies of binding of multisubstrate analogue inhibitor — 2-amino-9-[2-(phosphonomethoxy)ethyl]-6-sulfanylpurine

Cited by 10 publications

References 34 publications

Computational Methods for De novo Protein Design and its Applications to the Human Immunodeficiency Virus 1, Purine Nucleoside Phosphorylase, Ubiquitin Specific Protease 7, and Histone Demethylases

Computational Methods for De novo Protein Design and its Applications to the Human Immunodeficiency Virus 1, Purine Nucleoside Phosphorylase, Ubiquitin Specific Protease 7, and Histone Demethylases

Multisubstrate adduct inhibitors: Drug design and biological tools

Crystal structure ofEscherichia colipurine nucleoside phosphorylase complexed with acyclovir

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