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Last update 08 May 2025

Nudix motif protein

Last update 08 May 2025

Basic Info

Synonyms-

Introduction-

Drugs associated with Nudix motif protein

HG-1303

Target

Nudix motif protein

Mechanism

Nudix motif protein modulators

Active Org.-

Originator Org.

Human Genome Sciences, Inc.

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

HG-1211

Target

Nudix motif protein

Mechanism

Nudix motif protein modulators

Active Org.-

Originator Org.

Human Genome Sciences, Inc.

Active Indication-

Inactive Indication-

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with Nudix motif protein

100 Translational Medicine associated with Nudix motif protein

0 Patents (Medical) associated with Nudix motif protein

Literatures (Medical) associated with Nudix motif protein

31 Jan 2025·Journal of Bacteriology

An unusual activity of mycobacterial MutT1 Nudix hydrolase domain as a protein phosphatase regulates nucleoside diphosphate kinase function

Article

Author: Singh, Devendra Pratap ; Saini, Deepak K. ; Roy, Koyel ; Varshney, Umesh ; Emam, Elhassan Ali Fathi

ABSTRACT MutT proteins are Nudix hydrolases characterized by the presence of a Nudix box, GX5EX7REUXEEXGU, where U is a bulky hydrophobic residue and X is any residue. Major MutT proteins hydrolyze 8-oxo-(d)GTP (8-oxo-GTP or 8-oxo-dGTP) to the corresponding 8-oxo-(d)GMP, preventing their incorporation into nucleic acids. Mycobacterial MutT1 comprises an N-terminal domain (NTD) harboring the Nudix box motif, and a C-terminal domain (CTD) harboring the RHG histidine phosphatase motif. Interestingly, unlike other MutTs, the MutT1 hydrolyses the mutagenic 8-oxo-(d)GTP to the corresponding 8-oxo-(d)GDP. Nucleoside diphosphate kinase (NDK), a conserved protein, carries out reversible conversion of (d)NDPs to (d)NTPs through phospho-NDK (NDK- Pi ) intermediate. Recently, we showed that NDK- Pi converts 8-oxo-dGDP to 8-oxo-dGTP and escalates A to C mutations in a MutT-deficient Escherichia coli . We now show that both Mycobacterium tuberculosis MutT1 and Mycobacterium smegmatis MutT1, through their NTD (Nudix hydrolase motifs) function as protein phosphatase to regulate the levels of NDK- Pi and prevent it from catalyzing conversion of (d)NDPs to (d)NTPs (including conversion of 8-oxo-dGDP to 8-oxo-dGTP). To corroborate this function, we show that Msm MutT1 decreases A to C mutations in E. coli under the conditions of Eco NDK overexpression. IMPORTANCE MutT proteins, having a Nudix box domain, hydrolyze the mutagenic 8-oxo-dGTP to 8-oxo-dGMP. However, mycobacterial MutT (MutT1) comprises an N-terminal domain (NTD) harboring a Nudix box, and a C-terminal domain (CTD) harboring an RHG histidine phosphatase. Unlike other MutTs, mycobacterial MutT1 hydrolyses 8-oxo-dGTP to 8-oxo-dGDP. Nucleoside diphosphate kinase (NDK), a conserved protein, converts 8-oxo-dGDP to 8-oxo-dGTP through phospho-NDK (NDK- Pi ) intermediate and escalates A to C mutations. Here, we show that the mycobacterial MutT1 is unprecedented in that its NTD (Nudix box), functions as protein phosphatase to regulate NDK- Pi levels and prevents it from converting dNDPs to dNTPs (including 8-oxo-dGDP to 8-oxo-dGTP conversion). In addition, mycobacterial MutT1 decreases A to C mutations in Escherichia coli under the conditions of NDK overexpression.

01 May 2024·The Plant Cell

Nudix hydrolase 23 post-translationally regulates carotenoid biosynthesis in plants

Article

Author: Li, Li ; Zhou, Xuesong ; Lui, Andy ; Thannhauser, Theodore ; Dudareva, Natalia ; Yang, Yong ; Fish, Tara ; Rao, Sombir ; Wrightstone, Emalee ; Cao, Hongbo ; O’Hanna, Franz Joseph ; Cheng, Lailiang

AbstractCarotenoids are essential for photosynthesis and photoprotection. Plants must evolve multifaceted regulatory mechanisms to control carotenoid biosynthesis. However, the regulatory mechanisms and the regulators conserved among plant species remain elusive. Phytoene synthase (PSY) catalyzes the highly regulated step of carotenogenesis and geranylgeranyl diphosphate synthase (GGPPS) acts as a hub to interact with GGPP-utilizing enzymes for the synthesis of specific downstream isoprenoids. Here, we report a function of Nudix hydrolase 23 (NUDX23), a Nudix domain-containing protein, in post-translational regulation of PSY and GGPPS for carotenoid biosynthesis. NUDX23 expresses highly in Arabidopsis (Arabidopsis thaliana) leaves. Overexpression of NUDX23 significantly increases PSY and GGPPS protein levels and carotenoid production, whereas knockout of NUDX23 dramatically reduces their abundances and carotenoid accumulation in Arabidopsis. NUDX23 regulates carotenoid biosynthesis via direct interactions with PSY and GGPPS in chloroplasts, which enhances PSY and GGPPS protein stability in a large PSY–GGPPS enzyme complex. NUDX23 was found to co-migrate with PSY and GGPPS proteins and to be required for the enzyme complex assembly. Our findings uncover a regulatory mechanism underlying carotenoid biosynthesis in plants and offer promising genetic tools for developing carotenoid-enriched food crops.

29 Dec 2023·Journal of Biomolecular Structure and Dynamics

Molecular dynamics simulations reveal the impact of NUDT15 R139C and R139H variants in structural conformation and dynamics

Article

Author: Garcia-Marin, Javier ; Gómez-Rubio, Elena

NUDT15, also known as MTH2, is a member of the NUDIX protein family that catalyzes the hydrolysis of nucleotides and deoxynucleotides, as well as thioguanine analogues. NUDT15 has been reported as a DNA sanitizer in humans, and more recent studies have shown that some genetic variants are related to a poor prognosis in neoplastic and immunologic diseases treated with thioguanine drugs. Despite this, the role of NUDT15 in physiology and molecular biology is quite unclear, as is the mechanism of action of this enzyme. The existence of clinically relevant variants has prompted the study of these enzymes, whose capacity to bind and hydrolyze thioguanine nucleotides is still poorly understood. By using a combination of biomolecular modeling techniques and molecular dynamics, we have studied the monomeric wild type NUDT15 as well as two important variants, R139C and R139H. Our findings reveal not only how nucleotide binding stabilizes the enzyme but also how two loops are responsible for keeping the enzyme in a packed, close conformation. Mutations in α2 helix affect a network of hydrophobic and π-interactions that enclose the active site. This knowledge contributes to the understanding of NUDT15 structural dynamics and will be valuable for the design of new chemical probes and drugs targeting this protein.Communicated by Ramaswamy H. Sarma.

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Nudix motif protein

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