Studies on high molecular weight modifiers of the nonhyperbolic <i>V</i> versus [<i>S</i>] curves of DT‐diaphorase

Hollander, Per M.; Gatt, S

doi:10.1016/0014-5793(75)80972-0

Cited by 2 publications

(1 citation statement)

References 8 publications

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“…In 1958 Ernster and Navazio discovered the existence of a highly active oxidoreductase enzyme in the soluble fraction of rat liver homogenates (1). They named it DT diaphorase and subsequently Ernster and colleagues described its properties, in particular its kinetic activity and inhibition (2)(3)(4)(5)(6). The enzyme is now better known as NAD(P)H quinone oxidoreductase 1 (NQO1; EC 1.6.5.2).…”

Section: Structure and Functions Of Nqo1mentioning

confidence: 99%

Natural Small Molecules as Stabilizers and Activators of Cancer-Associated NQO1 Polymorphisms

Pey¹,

Megarity²,

Medina‐Carmona³

et al. 2016

CDT

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quinone oxidoreductase 1 (NQO1) is an antioxidant and detoxifying enzyme involved in the two-electron reduction of a wide variety of quinones. As a non-enzymatic function, it is involved in the stabilization of several tumour suppressors such as p53, p33 and p73α. NQO1 is overexpressed in several types of tumours, and two common polymorphisms are associated with increased cancer risk, making NQO1 a potential target for new cancer treatments. Here we review the structural and enzymological properties of NQO1, as well as its roles in cancer development and treatment. Particularly, we focus on recent developments on the understanding of the molecular basis leading to loss-of-function in cancer-associated polymorphisms, and propose new approaches to target these molecular defects to develop new pharmacological agents to rescue them. We will focus on pharmacological therapies aimed at correcting the abnormal properties of polymorphic proteins (such as protein stability and dynamics) and modulating intracellular factors leading to loss-of-function (such as accelerated proteasomal degradation).

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Section: Structure and Functions Of Nqo1mentioning

confidence: 99%

Natural Small Molecules as Stabilizers and Activators of Cancer-Associated NQO1 Polymorphisms

Pey¹,

Megarity²,

Medina‐Carmona³

et al. 2016

CDT

View full text Add to dashboard Cite

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Binding profile of quinonoid-dihydrobiopterin to quinonoid-dihydropteridine reductase examined by in silico and in vitro analyses

Kono

Hara

Furuta

et al. 2023

The Journal of Biochemistry

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Quinonoid dihydropteridine reductase (QDPR) catalyzes the reduction of quinonoid-form dihydrobiopterin (qBH2) to tetrahydrobiopterin (BH4). BH4 metabolism is a drug target for neglected tropical disorders, as trypanosomatid protozoans, including Leishmania and Trypanosoma, require exogenous sources of biopterin for growth. Although QDPR is a key enzyme for maintaining intracellular BH4 levels, the precise catalytic properties and reaction mechanisms of QDPR are poorly understood due to the instability of quinonoid-form substrates. In this study, we analyzed the binding profile of qBH2 to human QDPR in combination with in silico and in vitro methods. First, we performed docking simulation of qBH2 to QDPR to obtain possible binding modes of qBH2 at the active site of QDPR. Then, among them, we determined the most plausible binding mode using molecular dynamics simulations revealing its atomic-level interactions and confirmed it with the in vitro assay of mutant enzymes. Moreover, it was found that not only qBH2 but also quinonoid-form dihydrofolate (qDHF) could be potential physiological substrates for QDPR, suggesting that QDPR may be a bifunctional enzyme. These findings in this study provide important insights into biopterin and folate metabolism and would be useful for developing drugs for neglected tropical diseases.

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Studies on high molecular weight modifiers of the nonhyperbolic V versus [S] curves of DT‐diaphorase

Cited by 2 publications

References 8 publications

Natural Small Molecules as Stabilizers and Activators of Cancer-Associated NQO1 Polymorphisms

Natural Small Molecules as Stabilizers and Activators of Cancer-Associated NQO1 Polymorphisms

Binding profile of quinonoid-dihydrobiopterin to quinonoid-dihydropteridine reductase examined by in silico and in vitro analyses

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