Phosphoglycerate mutase catalyzes the interconversion between 2-phosphoglycerate and 3-phosphoglycerate in the glycolytic and gluconeogenic pathways. They exist in two unrelated forms, that is either cofactor (2,3-diphosphoglycerate) dependent or cofactor-independent. These two enzymes have no similarity in amino acid sequence, tertiary structure, and in catalytic mechanism. Wuchereria bancrofti (WB) contains the cofactor-independent form, whereas other organisms can possess the dependent form or both. Since, independent phosphoglycerate mutase (iPGM) is an essential gene for the survival of nematodes, and it has no sequence or structural similarity to the cofactor-dependent phosphoglycerate mutase found in mammals, it represents an attractive drug target for the filarial nematodes. In this current study, a putative cofactor-iPGM gene was identified in the protein sequence of the WB. In the absence of crystal structure, a three-dimensional structure was determined using the homology modeling approximation, and the most stable protein conformation was identified through the molecular dynamics simulation studies, using GROMACS 4.5. Further, the functional or characteristic residues were identified through the sequence analysis, potential inhibitors were short-listed and validated, and potential inhibitors were ranked using the cheminformatics and molecular dynamics simulations studies, Prime MM-GBSA approach, respectively.
:
RNA binding proteins (RBPs) associate with nascent and mature RNAs to perform biological functions such as
alternative splicing and RNA stability. Having unique RNA recognition binding motifs, RBPs form complexes with RNA
in a sequence- and structure-based manner. Aberrant expressions of several RBPs have been identified in tumorigenesis
and cancer progression. These uncontrolled RBPs affect several mechanisms, including cell proliferation, tumor growth,
invasion, metastasis and chemoresistance. Epithelial splicing regulatory protein 1 (ESRP1) is a member of the hnRNP
family of proteins that play a crucial role in regulating numerous cellular processes, including alternative splicing and
translation of multiple genes during organogenesis. Abnormal expression of ESRP1 alters the cell morphology, and leads
to cell proliferation and tumor growth during cancer progression. ESRP1 mediated alternative splicing of target genes,
including CD44, FGFR, PTBP1, LYN, ENAH, SPAG1 and ZMYND8, results in cancer progression. In addition, ESRP1
also regulates circularization and biogenesis of circular RNAs such as circUHRF1, circNOL10 and circANKS1B, whose
expressions have been identified as key factors in various cancers. This multi-functional protein is also involved in imposing stability of target mRNAs such as cyclin A2, and thereby cell cycle regulation. The scope of this review is to examine
recent scientific data, outcomes of the up- and down-regulated proteins, and the role of ESRP1 in various cancers. We
conclude by summarizing ESRP1 dysregulation and its consequences on target genes in various human cancers. Collectively, the consequences of ESRP1 mediated splicing in cancer cells suggest the role of ESRP1 in cell proliferation and
chemoresistance via apoptosis and autophagy modulation, which could therefore be potential targets for cancer therapeutics.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.