Biology subjects

Sethi, D.

Publications and source records attributed to Sethi, D..

4 recordsLinked to original sources

bioRxiv2025

Mapping the Metalloproteome of Deinococcus indicus DR1 through Integrative Structure and Function Annotation

Deinococcus indicus DR1 is a rod-shaped bacterium isolated from the Dadri wetlands (Uttar Pradesh, India) that tolerates ionizing radiation and arsenic. The molecular basis of its wider heavy-metal resilience, particularly among the 1017 out of 4128 proteins still annotated as hypothetical, remains unclear. We performed a proteome-wide structural and functional survey to address this gap. All the 4128 proteins were modeled with AlphaFold2, yielding very-high-confidence structures (pLDDT [≥] 90) for 2145 sequences. CATH/InterPro analysis assigned domains to 2735 proteins. Functions were predicted by combining DeepFRI (graph neural-network), MorphologFinder (Foldseek plus EggNOG-Mapper), and existing GenBank annotations. The integrated workflow suggests that more than 100 previously uncharacterized proteins may bind or transport arsenic, chromium, cobalt, copper, iron, manganese, molybdenum, nickel, or zinc, indicating a metal-handling capacity that extends beyond the known ars operon. Recurrent domain architectures that include P-loop NTPases, Rossmann folds, GNAT acetyl-transferases, and sensor modules (CHASE, PAS, GAF) point to coordinated redox regulation and efflux pathways. Twenty high-confidence metal-binding candidates have been prioritized for experimental validation through expression, mutagenesis, and knockout studies. All structural models, domain assignments, and query tools are available at https://deinococcus.in, providing a resource for future investigations of heavy-metal tolerance in this organism.

bioinformatics↗

bioRxiv2022

Characterisation of neonatal Staphylococcus capitis NRCS-A isolates compared with non NRCS-A Staphylococcus capitis from neonates and adults.

Staphylococcus capitis is a frequent cause of Late-Onset Sepsis (LOS) in neonates admitted to Neonatal Intensive Care Units (NICU). The NRCS-A clone of S. capitis has been isolated from NICUs globally although the reasons for the global success of this clone are not understood. We analysed a collection of S. capitis colonising babies admitted to two NICUs, one in the UK and one in Germany as well as corresponding pathological clinical isolates. Genome analysis identified 3 groups; non-NRCS-A isolates, NRCS-A isolates, and a group of proto NRCS-A - isolates closely related to NRCS-A but not associated with neonatal infection. All bloodstream isolates belonged to the NRCS-A group and were indistinguishable from strains carried on the skin or in the gut. NRCS-A isolates showed increased tolerance to chlorhexidine and antibiotics relative to the other S. capitis as well as enhanced ability to grow at higher pH values. Analysis of 138 pangenomes of the clades identified characteristic nsr and tarJ genes in the NRCS-A and proto groups with a CRISPR-cas system only seen in NRCS-A isolates which also showed enrichment of genes for metal acquisition and transport. We found evidence for transmission of S. capitis NRCS-A within NICU, with related isolates shared between babies and multiple acquisitions by some babies. Our data show NRCS-A strains commonly colonise uninfected babies in NICU representing a potential reservoir for potential infection. This work provides more evidence that adaptation to survive in the gut and on skin facilitates spread of NRCS-A, and that metal acquisition and tolerance may be important to the biology of NRCS-A. Understanding how NRCS-A survives in NICUs can help develop infection control procedures against this clone.

genomics↗

bioRxiv2021

Comparative analysis of Lysine and Arginine biosynthesis pathway in Deinococcus genomes

The members of the Deinococcaceae family have the ability to survive extreme environmental conditions. Deinococcus species have a complex cell envelope composed of L-ornithine containing peptidoglycan. Anabolism of L-ornithine is intrinsically linked to L-lysine and L-arginine biosynthetic pathways. To understand these two pathways, we analyzed the L-lysine and L-arginine pathways using 23 Deinococcus genomes, including D. indicus. We used BLAST-P based ortholog identification using D. radiodurans genes as the query. We identified some BLAST-P hits that shared the same functional annotation. We analyzed three (class I aminotransferase, acetyl-lysine deacetylase, and acetyl glutamate/acetyl aminoadipate kinase) from L-lysine biosynthesis pathway and three (bifunctional ornithine acetyltransferase or N-acetyl glutamate synthase protein, nitric oxide synthase-like protein, and Acetyl-lysine deacetylase) from L-arginine biosynthesis pathway. Two proteins showed certain structural variations. Specifically, [LysW]-lysine hydrolase proteins sequence and structure level changes indicated changes in oligomeric conformation, which could likely be a result of divergent evolution. And, bifunctional ornithine acetyltransferase or N-acetyl glutamate synthase had its active site pocket positions shifted at the structural level and we hypothesize that it may not perform at the optimal level. Thus, we were able to compare and contrast different Deinococcus species indicating some genes occurring because of divergent evolution.

bioinformatics↗

bioRxiv2017

Prediction of residue-residue contacts in CASP12 targets from its predicted tertiary structures

One of the challenges in the field of structural proteomics is to predict residue-residue contacts in a protein. It is an integral part of CASP competitions due to its importance in the field of structural biology. This manuscript describes RRCPred 2.0 a method participated in CASP12 and predicted residue-residue contact in targets with high precision. In this approach, firstly 150 predicted protein structures were obtained from CASP12 Stage 2 tarball and ranked using clustering-based quality assessment software. Secondly, residue-residue contacts were assigned in top 10 protein structures based on distance between residues. Finally, residue-residue contacts were predicted in target protein based on consensus/average in top 10 predicted structures. This simple approach performs better than most of CASP12 methods in the categories of TBM and TBM/FM. It ranked 1st in following categories; i) TBM domain on list size L/5, ii) TBM/FM domain on list size L/5 and iii) TBM/FM domain on Top 10. These observations indicate that predicted tertiary structure of a protein can be used for predicting residue-residue contacts in protein with high accuracy.

bioinformatics↗