Last update 19 Sep 2024

SMDT1

Last update 19 Sep 2024

Basic Info

Synonyms

C22orf32, DDDD, dJ186O1.1

+ [5]

Introduction

Essential regulatory subunit of the mitochondrial calcium uniporter complex (uniplex), a complex that mediates calcium uptake into mitochondria (PubMed:24231807, PubMed:26774479, PubMed:27099988). Required to bridge the calcium-sensing proteins MICU1 and MICU2 with the calcium-conducting subunit MCU (PubMed:24231807). Plays a central role in regulating the uniplex complex response to intracellular calcium signaling (PubMed:27099988). Acts by mediating activation of MCU and retention of MICU1 to the MCU pore, in order to ensure tight regulation of the uniplex complex and appropriate responses to intracellular calcium signaling (PubMed:27099988).

Drugs associated with SMDT1

NAV-205

Target

SMDT1

Mechanism

SMDT1 inhibitors

Active Org.

Navrogen, Inc.Startup

Originator Org.

Navrogen, Inc.Startup

Active Indication

Solid tumor

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with SMDT1

100 Translational Medicine associated with SMDT1

0 Patents (Medical) associated with SMDT1

320

Literatures (Medical) associated with SMDT1

01 Oct 2024·Bioelectrochemistry

Transporter function characterization via continuous-exchange cell-free synthesis and solid supported membrane-based electrophysiology

Article

Author: Bazzone, Andre ; Dong, Fang ; Lojko, Pawel ; Bernhard, Frank ; Borodina, Irina

Functional characterization of transporters is impeded by the high cost and technical challenges of current transporter assays. Thus, in this work, we developed a new characterization workflow that combines cell-free protein synthesis (CFPS) and solid supported membrane-based electrophysiology (SSME). For this, membrane protein synthesis was accomplished in a continuous exchange cell-free system (CECF) in the presence of nanodiscs. The resulting transporters expressed in nanodiscs were incorporated into proteoliposomes and assayed in the presence of different substrates using the surface electrogenic event reader. As a proof of concept, we validated this workflow to express and characterize five diverse transporters: the drug/H⁺-coupled antiporters EmrE and SugE, the lactose permease LacY, the Na⁺/H⁺ antiporter NhaA from Escherichia coli, and the mitochondrial carrier AAC2 from Saccharomyces cerevisiae. For all transporters kinetic parameters, such as K_M, I_MAX, and pH dependency, were evaluated. This robust and expedite workflow (e.g., can be executed within only five workdays) offers a convenient direct functional assessment of transporter protein activity and has the ability to facilitate applications of transporters in medical and biotechnological research.

01 Oct 2024·Environmental Technology

The genotoxicity impact of heavy metals on the Escherichia coli

Article

Author: Zheng, Xing ; Yang, Heyun ; Guo, Menghan ; Liu, Tong ; Bao, Dongguan

In present work, the genotoxicity of Hg²⁺, Ag⁺, Cr⁶⁺, Ni²⁺, Pb²⁺, Co²⁺, Mn²⁺, Zn²⁺, and Cr³⁺ was investigated via a quantitative toxicogenomics assay, to understand the toxic mechanism of heavy metals with greater depth. Under the experimental conditions, Hg²⁺, Ag⁺, and Cr⁶⁺ showed a more serious toxic impact on the expression of functional genes (eg., oxyR, katG, grxA, osmE, emrE, dinG) than Ni²⁺, Pb²⁺, Co²⁺, Mn²⁺, Zn²⁺, and Cr³⁺, while the protein, oxidative, and membrane stress response pathways were more sensitive to the toxicity of Hg²⁺, Ag⁺, and Cr⁶⁺ than the DNA and general stress response pathways. Compared with the other kinds of heavy metals, Ni²⁺, Pb²⁺, Co²⁺, and Mn²⁺ altered the expression of functional genes (uvrY, recX, mutY, and sbmC) related to the DNA stress response pathways more seriously, while Zn²⁺ and Cr³⁺ changed the expression of the functional genes (yfjG, ydgL, ssrA, and osmC) associated with the general stress response pathway more significantly. Meanwhile, the toxicity of Ni²⁺, Pb²⁺, Co²⁺, and Mn²⁺ was slightly higher than that of Zn²⁺ and Cr³⁺ in terms of the total value of transcriptional effect level Index (TELI) by detecting the promoter activities of different functional genes. In addition, to survive the toxicity of heavy metals, the expression of multidrug efflux genes (ydgL, cyoA, emrA, and emrE) and toxicity-resistant genes (Ion, dnaJ, clpB, mutY, dnaK, rpoD, sbmC) mainly functioned.

26 Aug 2024·Acta Microbiologica et Immunologica Hungarica

Genomic characterization of an uncommon Delftia acidovorans isolate obtained from a Bulgarian immunocompetent outpatient diagnosed with bronchitis

Article

Author: Strateva, Tanya ; Peykov, Slavil ; Atanasova, Svetlana ; Gergova, Raina ; Dimov, Svetoslav G.

AbstractDelftia acidovorans is an aerobic, non-fermenting Gram-negative bacterium (NFGNB), found in soil, water and hospital environments. It is rarely clinically significant, most commonly affecting hospitalized or immunocompromised patients. The present study aimed to explore the genomic characteristics of a Bulgarian clinical D. acidovorans isolate (designated Dac759) in comparison to all strains of this species with available genomes in the NCBI Genome database (n = 34). Dac759 was obtained in 2021 from the sputum of a 65-year-old female immunocompetent outpatient with bronchitis. Species identification using MALDI-TOF mass spectrometry, antimicrobial susceptibility testing, whole-genome sequencing (WGS), and phylogenomic analysis were performed. The isolate demonstrated high-level resistance to colistin (16 mg L−1); resistance to gentamicin; reduced susceptibility to piperacillin, piperacillin-tazobactam, ceftazidime, cefepime, ciprofloxacin, and levofloxacin; and susceptibility to imipenem, meropenem, amikacin, and tobramycin. The observed genome size (6.43 Mb) and GC content (66.76%) were comparable with the accessible data from sequenced D. acidovorans genomes. A limited number of resistance determinants were identified in the assembled genome as follows: blaOXA-459, emrE, oqxB, and mexCD-oprJ. The phylogenomic analysis indicated a high heterogenicity of the included D. acidovorans genomes. In conclusion, to the best of our knowledge, this is the first documented case of a clinically relevant D. acidovorans isolate in Bulgaria. Unlike the majority of reports in the literature, Dac759 affected a patient with no malignancies or other preexisting comorbidities. With this in mind, its genome sequence is a valuable resource for the fundamental study of uncommon bacterial pathogens of public health importance.

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SMDT1

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