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Title: An inter-switch between hydrophobic and charged amino acids generated druggable small molecule binding pocket in chemokine paralog CXCL3
Authors: Gulati K.
Gangele K.
Kumar D.
Poluri, Krishna Mohan
Published in: Archives of Biochemistry and Biophysics
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 ?-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. © 2018 Elsevier Inc.
Citation: Archives of Biochemistry and Biophysics(2019), 662(): 121-128
Issue Date: 2019
Publisher: Academic Press Inc.
Keywords: 8-Anilinonaphthalene-1-sulfonic acid
Growth related oncogene chemokines
Molecular evolution
Paralog proteins
ISSN: 39861
Author Scopus IDs: 56998446900
Author Affiliations: Gulati, K., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India
Gangele, K., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India
Kumar, D., Centr
Funding Details: KMP acknowledges the receipt of DBT-IYBA-BT/07/IYBA/2013-19 , and SERB-SB/YS/LS-380/2013 grants from Government of India . KG and KK acknowledge the MHRD fellowship from IIT-Roorkee. The authors thank Mr. Nipanshu Agarwal and Ms. Sharanya Sarkar for techn
Corresponding Author: Poluri, K.M.; Department of Biotechnology, Indian Institute of Technology Roorkee (IIT-Roorkee)India; email:
Appears in Collections:Journal Publications [BT]

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