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Citation
Tags
HERO ID
5018072
Reference Type
Journal Article
Title
An inter-switch between hydrophobic and charged amino acids generated druggable small molecule binding pocket in chemokine paralog CXCL3
Author(s)
Gulati, K; Gangele, K; Kumar, D; Poluri, KM
Year
2019
Is Peer Reviewed?
Yes
Journal
Archives of Biochemistry and Biophysics
ISSN:
0003-9861
EISSN:
1096-0384
Volume
662
Page Numbers
121-128
Language
English
PMID
30528777
DOI
10.1016/j.abb.2018.12.007
Web of Science Id
WOS:000457352100014
URL
https://www.proquest.com/scholarly-journals/inter-switch-between-hydrophobic-charged-amino/docview/2221061207/se-2?accountid=171501
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Abstract
Multigene families such as chemokines arose as a result of gene duplication events, followed by mutations and selection. GRO chemokines are three duplicated CXCL genes, comprising of CXCL1, CXCL2 and CXCL3 proteins. Comparative structural analysis of the two closely related paralog chemokines CXCL2 and CXCL3 in the current study indicated a variable electrostatic surface between them, and a specific hydrophobic pocket on the surface of CXCL3 that can bind naphthalene derivatives. Combined fluorescence and NMR analyses revealed that CXCL3 monomer can specifically bind to ANS (8-Anilinonaphthalene-1-sulfonic acid) with a stoichiometry of 1:1 by involving the residues belonging to the structural elements 310 helix and the α-helix. A close observation of the surfaces of these paralogs suggested that such a hydrophobic pocket is a resultant of inter-switch between a charged and a hydrophobic residue on the primary sequence of the two paralog proteins. Interestingly, the hydrophobic pocket is in the vicinity of GAG binding region of CXCL3, a molecular determinant in leukocyte trafficking. Such unique pockets/patches on specific chemokine surfaces can be exploited to design the naphthalene/small molecule based inhibitors against GAG binding to regulate their molecular interactions during the onset and progression of various types of cancers and inflammatory diseases.
Keywords
8-Anilinonaphthalene-1-sulfonic acid; Growth related oncogene chemokines; Molecular evolution; Paralog proteins; article; amino acids; chemokine CXCL1; chemokine CXCL2; chemokine CXCL3; fluorescence; gene duplication; hydrophobicity; multigene family; mutation; naphthalene; neoplasms; nuclear magnetic resonance spectroscopy; proteins; stoichiometry
Tags
IRIS
•
Naphthalene
Database Searches
PubMed
Combined data set
Data set for title/abstract screening
Excluded - PECO criteria not met (TIAB)
Feb 2019 Update
PubMed
Other
•
Naphthalene (2021 Evidence mapping publication)
Database Searches
PubMed
Combined data set
Data set for title/abstract screening
Excluded – PECO criteria not met
Feb 2019 Update
PubMed
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