Last update 01 Nov 2024

DHTKD1

Last update 01 Nov 2024

Basic Info

Synonyms

2-oxoadipate dehydrogenase complex component E1, 2-oxoadipate dehydrogenase, mitochondrial, Alpha-KADH-E1

+ [12]

Introduction

2-oxoadipate dehydrogenase (E1a) component of the 2-oxoadipate dehydrogenase complex (OADHC) (PubMed:29191460, PubMed:29752936, PubMed:32303640, PubMed:32633484, PubMed:32695416). Participates in the first step, rate limiting for the overall conversion of 2-oxoadipate (alpha-ketoadipate) to glutaryl-CoA and CO(2) catalyzed by the whole OADHC (PubMed:29191460, PubMed:32695416). Catalyzes the irreversible decarboxylation of 2-oxoadipate via the thiamine diphosphate (ThDP) cofactor and subsequent transfer of the decarboxylated acyl intermediate on an oxidized dihydrolipoyl group that is covalently amidated to the E2 enzyme (dihydrolipoyllysine-residue succinyltransferase or DLST) (Probable) (PubMed:29752936, PubMed:32303640, PubMed:32633484). Can catalyze the decarboxylation of 2-oxoglutarate in vitro, but at a much lower rate than 2-oxoadipate (PubMed:29191460, PubMed:29752936, PubMed:32633484, PubMed:32695416). Responsible for the last step of L-lysine, L-hydroxylysine and L-tryptophan catabolism with the common product being 2-oxoadipate (Probable).

Drugs associated with DHTKD1

WO2024139235

Patent Mining

Target

DHTKD1

Mechanism-

Active Org.

Xuzhou Medical University

Originator Org.

Xuzhou Medical University

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

CN116590242

Patent Mining

Target

DHTKD1

Mechanism-

Active Org.

Academy of Military Medical Sciences

Originator Org.

Academy of Military Medical Sciences

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

CN116478938

Patent Mining

Target

DHTKD1

Mechanism-

Active Org.

Sichuan University

Originator Org.

Sichuan University

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with DHTKD1

100 Translational Medicine associated with DHTKD1

0 Patents (Medical) associated with DHTKD1

3,446

Literatures (Medical) associated with DHTKD1

01 Nov 2024·Pediatric Blood & Cancer

Successful treatment of young childhood standard-risk hepatoblastoma with cisplatin monotherapy using a central review system.

Article

Author: Kaneda, Hide ; Fujimura, Junya ; Kazama, Takuro ; Takama, Yuichi ; Yoshimura, Kenichi ; Iehara, Tomoko ; Yamada, Yohei ; Hiyama, Eiso ; Kurihara, Sho ; Tanaka, Yukichi ; Takimoto, Tetsuya ; Nogami, Yuki ; Ida, Kohmei ; Hanaki, Ryo ; Nomura, Motonari ; Matsumura, Risa ; Miyazaki, Osamu ; Yokoi, Akiko ; Hishiki, Tomoro ; Mori, Makiko ; Honda, Shohei ; Saeki, Isamu ; Sekiguchi, Masahiro ; Inoue, Takeshi ; Kitagawa, Norihiko ; Watanabe, Kenichiro ; Nagase, Hiroki

BACKGROUNDThe JPLT3-S (Japanese Study Group for Pediatric Liver Tumors-3) study, conducted cisplatin (CDDP) monotherapy for young children (<3 years old) with standard-risk hepatoblastoma (HB) using a central review system in Japan. In the previous JPLT2 study, cases with resectable tumors without any annotation factors in the PRETEXT (PRETreatment EXTent of disease) classification (standard-risk HB) showed favorable outcomes with treatment consisting of CDDP and pirarubicin, but showed toxicities and late complications. In the JPLT3-S trial, a less intense regimen consisting of CDDP alone was evaluated.METHODSPatients who were less than 3 years of age and with PRETEXT I, II, or III HB without any annotation factors (e.g., E1, E1a, E2, E2a, H1, N1, P2, P2a, V3, and V3a) were eligible for inclusion in this study. In this trial, the central radiological and pathological features of all patients were reviewed. The primary outcome was the 3-year progression-free survival (PFS).RESULTSA total of 38 patients (23 female) were included. The median patient age was 12 months (range: 2-34). Two patients discontinued treatment because of progressive disease, and five patients discontinued treatment for other reasons. The 3-year PFS rate was 93.9% (95% confidence interval [CI]: 86.4%-100%). All 38 patients survived (follow-up period 38-98 months), and the OS rate was 100% (CI: 100). Eighteen of the 38 patients (47.4%) experienced ototoxicity as a late complication.CONCLUSIONCDDP monotherapy regimen is feasible in young patients with localized HB, as classified by a central review.

29 Oct 2024·mSphere

Preexisting cell state rather than stochastic noise confers high or low infection susceptibility of human lung epithelial cells to adenovirus

Article

Author: Petkidis, Anthony ; Greber, Urs F. ; Andriasyan, Vardan ; Suomalainen, Maarit ; Singh, Abhyudai

ABSTRACTViruses display large variability across all stages of their life cycle, including entry, gene expression, replication, assembly, and egress. We previously reported that the immediate early adenovirus (AdV) E1A transcripts accumulate in human lung epithelial A549 cancer cells with high variability, mostly independent of the number of incoming viral genomes, but somewhat correlated to the cell cycle state at the time of inoculation. Here, we leveraged the classical Luria–Delbrück fluctuation analysis to address whether infection variability primarily arises from the cell state or stochastic noise. The E1A expression was measured by the expression of green fluorescent protein (GFP) from the endogenous E1A promoter in AdV-C5_E1A-FS2A-GFP and found to be highly correlated with the viral plaque formation, indicating reliability of the reporter virus. As an ensemble, randomly picked clonal A549 cell isolates displayed significantly higher coefficients of variation in the E1A expression than technical noise, indicating a phenotypic variability larger than noise. The underlying cell state determining infection variability was maintained for at least 9 weeks of cell cultivation. Our results indicate that preexisting cell states tune adenovirus infection in favor of the cell or the virus. These findings have implications for antiviral strategies and gene therapy applications.IMPORTANCEViral infections are known for their variability. Underlying mechanisms are still incompletely understood but have been associated with particular cell states, for example, the eukaryotic cell division cycle in DNA virus infections. A cell state is the collective of biochemical, morphological, and contextual features owing to particular conditions or at random. It affects how intrinsic or extrinsic cues trigger a response, such as cell division or anti-viral state. Here, we provide evidence that cell states with a built-in memory confer high or low susceptibility of clonal human epithelial cells to adenovirus infection. Results are reminiscent of the Luria–Delbrück fluctuation test with bacteriophage infections back in 1943, which demonstrated that mutations, in the absence of selective pressure prior to infection, cause infection resistance rather than being a consequence of infection. Our findings of dynamic cell states conferring adenovirus infection susceptibility uncover new challenges for the prediction and treatment of viral infections.

12 Oct 2024·Journal of Biomolecular Structure and Dynamics

Computational identification and molecular dynamics simulation of potential circularRNA derived peptide from gene expression profile of Rheumatoid arthritis, Alzheimer’s disease, and Atrial fibrillation

Article

Author: Jayaraman, Manikandan ; Panchalingam, Santhiya ; Kasivelu, Govindaraju

The two most serious global health challenges confronting human society today are autoimmune disorders (AIDs) and neurological diseases (NDs), both of which shorten people's lives and worsen the situation. Despite their extensive impact, statistics show that AIDs is associated with a higher risk of ND. Circular RNAs (circRNAs) are critical in several illnesses and disorders, especially AID and ND. Therefore, the present study focused on understanding the underlying causes of the pathophysiology of diseases such as AID and ND through in silico-based research. In order to determine how circRNAs are related to various disease pathways, this study examined the gene expression data sets for Rheumatoid arthritis (RA), Alzheimer's disease (AD), and atrial fibrillation (AF). Our study identified and analyzed two circRNAs, their respective host genes (DHTKD1 and RAN) and their related miRNAs, which could serve as potential markers for treating disorders like myotonic dystrophy type 1, spinocerebellar ataxia and fragile X syndrome. Further, the circRNA-derived peptide was identified and analysed with the molecular dynamics simulation (MDS) followed by a principal component (PC) based free energy landscape (FEL) profile. The computational results obtained here provide a basis for the development of therapeutics against AD, RA and AF. Moreover, further functional studies are needed to validate their role in disease aetiology and to provide a detailed understanding of their association with AID and ND.Communicated by Ramaswamy H. Sarma.

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DHTKD1

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