DRG1

Last update 23 Jan 2025

Basic Info

Synonyms

developmentally regulated GTP binding protein 1, Developmentally-regulated GTP-binding protein 1, DRG-1

+ [6]

Introduction

Catalyzes the conversion of GTP to GDP through hydrolysis of the gamma-phosphate bond in GTP (PubMed:29915238, PubMed:23711155). Appears to have an intrinsic GTPase activity that is stimulated by ZC3H15/DFRP1 binding likely by increasing the affinity for the potassium ions (PubMed:23711155). When hydroxylated at C-3 of 'Lys-22' by JMJD7, may bind to RNA and play a role in translation (PubMed:19819225, PubMed:29915238). Binds to microtubules and promotes microtubule polymerization and stability that are required for mitotic spindle assembly during prophase to anaphase transition. GTPase activity is not necessary for these microtubule-related functions (PubMed:28855639).

100 Clinical Results associated with DRG1

100 Translational Medicine associated with DRG1

0 Patents (Medical) associated with DRG1

Literatures (Medical) associated with DRG1

01 Nov 2024·Structure

Rewiring protein binding specificity in paralogous DRG/DFRP complexes

Article

Author: Coleman, Mathew L ; Westrip, Christian A E ; Westrip, Christian A.E. ; Smerdon, Stephen J ; Coleman, Mathew L. ; Smerdon, Stephen J.

Eukaryotes have two paralogous developmentally regulated GTP-binding (DRG) proteins: DRG1 and DRG2, both of which have a conserved binding partner called DRG family regulatory protein 1 and 2 (DFRP1 and DFRP2), respectively. DFRPs are important for the function of DRGs and interact with their respective DRG via a conserved region called the DFRP domain. Despite being highly similar, DRG1 and DRG2 have strict binding specificity for their respective DFRP. Using AlphaFold generated structure models of the human DRG/DFRP complexes, we have biochemically characterized their interactions and identified interface residues involved in determining specificity. This analysis revealed that as few as five mutations in DRG1 can switch binding from DFRP1 to DFRP2. Moreover, while DFRP1 binding confers increased stability and GTPase activity to DRG1, DFRP2 binding only supports increased stability. Overall, this work provides new insight into the structural determinants responsible for the binding specificities of the DRG/DFRP complexes.

01 Oct 2024·Chemical Biology & Drug Design

Anti‐metastatic Effects of Bee Venom and Melittin in Breast Cancer Cells by Upregulation of BRMS1 and DRG1 Genes

Article

Author: Sivri, Nur Sena ; Kolayli, Sevgi ; Tetikoğlu, Sinan ; Çelik Uzuner, Selcen ; Farooqi, Ammad Ahmad

ABSTRACTApitherapy has started to gain tremendous recognition because of extraordinary pharmacological importance of honeybee‐related ingredients and their derivatives. There has been a renewed interest in the bee venom–based therapies. Interdisciplinary researchers are studying the chemistry and translational value of venom for effective cancer treatment. Bee venom and its major component, melittin, are cytotoxic in cancer cells. In this study, MTT and scratch assays were performed for analysis of melittin‐mediated antimetastatic effects. QPCR was used for expression profiling of metastasis‐related genes. Three anti‐metastatic genes (BRMS1, DRG1, and KAI1/CD82) were studied for the first time after bee venom and melittin treatment in MDA‐MB‐231 breast cancer cells compared with normal breast cells, and two prometastatic genes (EGFR and WNT7B) were also examined. KAI1/CD82 and BRMS1 are the negative regulators of EGFR. WNT7B is a negative regulator of KAI1/CD82. Selective cytotoxicity of bee venom and melittin was found to be higher as compared to cisplatin. Melittin induced an increase in the expression of BRMS1 and DRG1, whereas bee venom upregulated DRG1 and KAI1/CD82 expression in breast cancer. WNT7B was downregulated in bee venom–treated breast cancer cells. Results suggested that bee venom/melittin exerted antimetastatic effects primarily through upregulation of BRMS1, DRG1, and KAI1/CD82, and downregulation of WNT7B.

01 Oct 2024·Protein Science

Substrate selectivity and inhibition of the human lysyl hydroxylase JMJD7

Article

Author: Schofield, Christopher J. ; Bilgin, Nurgül ; Salah, Eidarus ; Wang, Yicheng ; Al‐Salmy, Aziza ; Dhingra, Siddhant ; Mecinović, Jasmin ; Martín, Sandra Pinzón ; Tumber, Anthony

AbstractJumonji‐C (JmjC) domain‐containing protein 7 (JMJD7) is a human Fe(II) and 2‐oxoglutarate dependent oxygenase that catalyzes stereospecific C3‐hydroxylation of lysyl‐residues in developmentally regulated GTP binding proteins 1 and 2 (DRG1/2). We report studies exploring a diverse set of lysine derivatives incorporated into the DRG1 peptides as potential human JMJD7 substrates and inhibitors. The results indicate that human JMJD7 has a relatively narrow substrate scope beyond lysine compared to some other JmjC hydroxylases and lysine‐modifying enzymes. The geometrically constrained (E)‐dehydrolysine is an efficient alternative to lysine for JMJD7‐catalyzed C3‐hydroxylation. γ‐Thialysine and γ‐azalysine undergo C3‐hydroxylation, followed by degradation to formylglycine. JMJD7 also catalyzes the S‐oxidation of DRG1‐derived peptides possessing methionine and homomethionine residues in place of lysine. Inhibition assays show that DRG1 variants possessing cysteine/selenocysteine instead of the lysine residue efficiently inhibit JMJD7 via cross‐linking. The overall results inform on the substrate selectivity and inhibition of human JMJD7, which will help enable the rational design of selective small‐molecule and peptidomimetic inhibitors of JMJD7.

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DRG1

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