C19orf48

Last update 08 May 2025

Basic Info

Synonyms

BC006151, C19orf48, chromosome 19 open reading frame 48

+ [3]

Introduction-

100 Clinical Results associated with C19orf48

100 Translational Medicine associated with C19orf48

0 Patents (Medical) associated with C19orf48

590

Literatures (Medical) associated with C19orf48

03 May 2025·Journal of Biomolecular Structure and Dynamics

Comprehending conformational changes in EmrE, multidrug transporter at different pH: insights from molecular dynamics simulations

Article

Author: Kaur, Manpreet ; Arya, Preeti ; Singh, Balvinder ; Chosyang, Stanzin

EmrE is a small multidrug resistance (SMR) pump of antiparallel topology that confers resistance to a broad range of polyaromatic cations in Escherichia coli. Atomic-level understanding of conformational changes for the selectivity of substrate and transport of a diverse array of drugs through the smallest known efflux pumps is crucial to multi-drug resistance. Therefore, the present study aims to provide insights into conformational changes during the transport through EmrE transporter at different pH. Molecular dynamics simulations have been carried out on the complete structure of EmrE in the absence of substrate. Computational analyses such as secondary structure, principal component, dynamic cross-correlation matrix, and hydrogen bond calculations have been performed. Analysis of MD trajectories in this study revealed pH-dependent interactions that influenced the structural dynamics of EmrE. Notably, at high pH, Glu14 and Tyr60 in both monomers formed electrostatic interactions, while these interactions decreased significantly at a low pH. Interestingly, a kink at helix 3 (H3) and dual open conformation of EmrE at low pH were also observed in contrast to a closed state discerned towards the periplasmic side at high pH. Significant interactions between C-terminal residues and residues at the edge of H1 & Loop1 and H3 & Loop3 were identified, suggesting their role in stabilizing the closed conformation of EmrE at the periplasmic end under high pH conditions. The present study enhances our understanding of EmrE's conformational changes, shedding light on the pH-dependent mechanisms that are likely to impact its function in multi-drug resistance.

01 Apr 2025·Journal of Molecular Biology

Conversion of Human Multidrug Transporter P-glycoprotein (ABCB1) from Drug Efflux to Uptake Pump: Evidence for a Switch Region Modulating the Direction of Substrate Transport

Article

Author: Ranganathan, Nandhini ; Ahmed, Shafaq ; Durell, Stewart R ; Sajid, Andaleeb ; Ambudkar, Suresh V ; Guha, Rajan ; Murakami, Megumi

The multidrug transporter P-glycoprotein (P-gp), is pivotal in exporting various chemically dissimilar amphipathic compounds including anti-cancer drugs, thus causing multidrug resistance during cancer treatment. P-gp is composed of two transmembrane domains (TMDs), each containing six homologous transmembrane helices (TMHs). Among these helices, TMH 6 and 12 align oppositely, lining a drug-binding pocket in the transmembrane region which acts as a pathway for drug efflux. Previously, we demonstrated that specific mutations within TMH 6 and 12 resulted in loss of substrate efflux and altered the transport direction from efflux to uptake for some substrates. This suggested the presence of a regulatory switch that governs the direction of transport. In this study, we sought to elucidate the mechanism of switch region modulation of the uptake function by engineering several mutants via substituting specific residues in TMH 6 and 12. We discovered that the alanine substitution of four residues (V974, L975, V977, and F978) within the upper region of TMH 12, along with three residues (V334, F336, and F343) within TMH 6, was sufficient to convert P-gp from an efflux to an uptake pump. Additional mutagenesis of the residues in the middle region of TMH 12 revealed that the uptake function, like efflux, is reversible. Further studies, including molecular dynamics simulations, revealed that the switch region appears to act during the substrate translocation step. We propose that the switch region in TMH 6 and 12, which modulates the direction of transport by P-gp, provides a novel approach to selectively target P-gp-expressing cancer cells.

01 Mar 2025·Journal of Global Antimicrobial Resistance

Nationwide phylogenomic surveillance of Mycobacterium tuberculosis in Mexico reveals pathogenic and drug resistant signatures of the prevailing L4 sublineage

Article

Author: Martinez-Urtaza, Jaime ; Garcia-Ulloa, Manuel ; Martinez-Guarneros, Armando ; Vazquez-Chacon, Carlos A ; Alvarez-Maya, Ikuri

BACKGROUNDTuberculosis disease is a major global health concern. In Mexico, information regarding the genomic variants of Mycobacterium tuberculosis (MTB) prevailing in the country and the existence of specific biogeographical patterns remains extremely scarce.OBJECTIVEThis study aimed to identify the genotypic patterns of MTB isolates in Mexico and determine the genes and specific single nucleotide polymorphisms involved in the evolution of these populations.METHODSPhylogenomic and pan-genomic analyses were performed using publicly available Mexican MTB genomes along with 33 newly sequenced genomes from Jalisco, considering a global context.RESULTSThe L4 sublineages of MTB, such as L4.1.1 (X), L4.1.2 (H), and L4.3 (LAM), were the most prevalent in Mexico. We found exclusive mutations and gene clusters in a virulent sublineage L4.1.1.3 (X3), which is endemic to Mexico. These genes encoded three PE/PPE family proteins: a multidrug transporter, thioredoxin domain-containing protein, quinone-dependent l-lactate dehydrogenase, DUF1725 domain-containing protein, amidase, poly (A) polymerase, and six hypothetical/uncharacterised proteins. Additionally, the genes encode an ESX-1 secretion-associated protein and a deazaflavin-dependent nitroreductase (ddn).CONCLUSIONX3 was distinguished from the rest of the sublineages by containing genes related to pathogenicity and virulence, as well as a gene linked to delamanid, an antibiotic for active multidrug-resistant tuberculosis. These findings provide valuable insight into the circulation and spread of MTB in Mexico.

Analysis

Perform a panoramic analysis of this field.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

C19orf48

Basic Info

Related

Analysis