Identification and functional annotation of hypothetical proteins of uropathogenic Escherichia coli strain CFT073 towards designing antimicrobial drug targets. Issue 24 (26th December 2022)

• Record Type: Journal Article
• Authors: Kaur, Harpreet; Singh, Vikram; Kalia, Manmohit; Mohan, Balvinder; Taneja, Neelam
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 40:Issue 24(2022)
• Page Start: 14084
• Page End: 14095
• Publication Date: 2022-12-26
• Subjects: Uropathogenic -- Escherichia coli -- hypothetical proteins -- functional annotation -- in-silico analysis -- drug targets; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2021.2000499
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract: Urinary tract infections are a serious health concern worldwide, especially in developing countries. Escherichia coli strain CFT073 is a highly virulent pathogenic bacterial strain. CFT073 proteome contains 4897 proteins, out of which 992 have been classified as hypothetical proteins. Identification and characterization of hypothetical proteins can aid in the selection of targets for drug design. In this study, we studied the hypothetical proteins from the UPEC strain CFT073 using various computational tools. By NCBI-CDD, 376 protein sequences showed conserved domains. Based on the functional motifs in their primary sequences, we classified these 376 hypothetical proteins into 7 functional categories. Further KEGG database was used to find the roles of these hypothetical proteins in several pathways. Protein interaction network analysis of hypothetical proteins identified 53 proteins as highly interacting metabolic proteins. Virulence factor analysis of the proteins identified 8 proteins as virulent. We conducted a non-homology search for the identified proteins of UPEC in the available human proteome. We observed that 35 proteins are non-homologous to humans and hence could be selected for drug designing targets. Qualitative characterization of the selected 35 non-homologous hypothetical proteins including essentiality analysis and evaluation of druggability by similarity search against drug bank database was performed. Out of these 35 proteins, three-dimensional structures of six proteins (NP_752562.1, NP_756345.1, NP_754893.1, NP_756600.2, NP_755264.1 and NP_752994.1) could be successfully modelled. These new annotations can help to better understand disease mechanisms at the molecular level, as well as provide new targets for drug development against the UPEC strain CFT073. Communicated by Ramaswamy H. Sarma