Skip navigation
Please use this identifier to cite or link to this item: http://repository.iitr.ac.in/handle/123456789/26964
Title: Crystal structure of a novel regulatory 40-kDa mammary gland protein (MGP-40) secreted during involution
Authors: Mohanty A.K.
Singh G.
Paramasivam M.
Saravanan K.
Jabeen T.
Sharma S.
Yadav S.
Kaur P.
Kumar, Pravindra R.Manish
Srinivasan A.
Singh T.P.
Published in: Journal of Biological Chemistry
Abstract: We have determined the crystal structure of a novel regulatory protein (MGP-40) from the mammary gland. This protein is implicated as a protective signaling factor that determines which cells are to survive the drastic tissue remodeling that occurs during involution. It has been indicated that certain cancers could surreptitiously utilize the proposed normal protective signaling by proteins of this family to extend their own survival and thereby allow them to invade the organ and metastasize. In view of this, MGP-40 could form an important target for rational structure-based drug design against breast cancer. It is a single chain, glycosylated protein with a molecular mass of 40 kDa. It was isolated from goat dry secretions and has been cloned and sequenced. It was crystallized by microdialysis from 20 mg ml-1 solution in 0.1 M Tris-HCl, pH 8.0, and equilibrated against the same solution containing 19% ethanol. Its x-ray structure has been determined by molecular replacement and refined to a 2.9 A resolution. The protein adopts a β/α domain structure with a triose-phosphate isomerase barrel conformation in the core and a small α+β folding domain. A single glycosylation site containing two N-acetylglucosamine units has been observed in the structure. Compared with chitinases and chitinase-like proteins the most important mutation in this protein pertains to a change from Glu to Leu at position 119, which is part of the so-called active site sequence in the form of Asp115, Leu119, and Asp186 and in this case resulting in the loss of chitinase activity. The orientations of two Trp residues Trp78 and Trp331 in the β barrel reduces the free space, drastically impairing the binding of saccharides/polysaccharides. However, the site and mode of binding of this protein to cell surface receptors are not yet known.
Citation: Journal of Biological Chemistry, 278(16): 14451-14460
URI: https://doi.org/10.1074/jbc.M208967200
http://repository.iitr.ac.in/handle/123456789/26964
Issue Date: 2003
Keywords: Cells
Crystal structure
Ethanol
Polysaccharides
Proteins
Solutions
Tumors
Regulatory proteins
Biochemistry
alcohol
aspartic acid
chitinase
glutamic acid
leucine
mammary gland protein 40
n acetylglucosamine
regulator protein
tryptophan
unclassified drug
alcohol
antineoplastic agent
glycoprotein
amino acid substitution
animal tissue
article
breast
breast cancer
cell survival
crystal structure
drug design
enzyme activity
glycosylation
involution
metastasis
molecular cloning
molecular weight
mutation
nonhuman
nucleotide sequence
priority journal
protein binding
protein domain
protein folding
protein secretion
protein structure
sequence analysis
signal transduction
amino acid sequence
animal
apoptosis
binding site
breast tumor
chemical structure
chemistry
electron
goat
metabolism
molecular genetics
nucleotide sequence
pH
physiology
protein conformation
protein secondary structure
protein tertiary structure
sequence homology
spectrofluorometry
X ray crystallography
Animalia
Capra hircus
Amino Acid Sequence
Animals
Antineoplastic Agents
Apoptosis
Base Sequence
Binding Sites
Breast
Breast Neoplasms
Crystallography, X-Ray
Electrons
Ethanol
Glycoproteins
Glycosylation
Goats
Hydrogen-Ion Concentration
Models, Molecular
Molecular Sequence Data
Mutation
Protein Binding
Protein Conformation
Protein Folding
Protein Structure, Secondary
Protein Structure, Tertiary
Sequence Homology, Amino Acid
Spectrometry, Fluorescence
ISSN: 219258
Author Scopus IDs: 7102044473
57213799551
6701391680
57215459017
8505192500
7405881718
37162551900
7102359516
55064809000
7202314476
57218945130
Author Affiliations: Mohanty, A.K., Department of Biophysics, All India Inst. of Medical Sciences, New Delhi 110 029, India
Singh, G., Department of Biophysics, All India Inst. of Medical Sciences, New Delhi 110 029, India
Paramasivam, M., Department of Biophysics, All India Inst. of Medical Sciences, New Delhi 110 029, India
Saravanan, K., Department of Biophysics, All India Inst. of Medical Sciences, New Delhi 110 029, India
Jabeen, T., Department of Biophysics, All India Inst. of Medical Sciences, New Delhi 110 029, India
Sharma, S., Department of Biophysics, All India Inst. of Medical Sciences, New Delhi 110 029, India
Yadav, S., Department of Biophysics, All India Inst. of Medical Sciences, New Delhi 110 029, India
Kaur, P., Department of Biophysics, All India Inst. of Medical Sciences, New Delhi 110 029, India
Kumar, P., Department of Biophysics, All India Inst. of Medical Sciences, New Delhi 110 029, India
Srinivasan, A., Department of Biophysics, All India Inst. of Medical Sciences, New Delhi 110 029, India
Singh, T.P., Department of Biophysics, All India Inst. of Medical Sciences, New Delhi 110 029, India
Funding Details: 
Corresponding Author: Singh, T.P.; Department of Biophysics, , New Delhi 110 029, India; email: tps@aiims.aiims.ac.in
Appears in Collections:Journal Publications [BT]

Files in This Item:
There are no files associated with this item.
Show full item record


Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.