1LJY

Crystal Structure of a Novel Regulatory 40 kDa Mammary Gland Protein (MGP-40) secreted during Involution

Summary for 1LJY

• Entry DOI: 10.2210/pdb1ljy/pdb
• Descriptor: MGP-40, 2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: mammary gland protein, marker protein, cancer regressor protein, signaling protein
• Biological source: Capra hircus (goat)
• Total number of polymer chains: 1
• Total formula weight: 41010.20

Authors

Mohanty, A.K.,Singh, G.,Paramasivam, M.,Saravanan, K.,Jabeen, T.,Sharma, S.,Yadav, S.,Kaur, P.,Kumar, P.,Srinivasan, A.,Singh, T.P. (deposition date: 2002-04-23, release date: 2003-03-18, Last modification date: 2024-10-30)

Primary citation

Mohanty, A.K.,Singh, G.,Paramasivam, M.,Saravanan, K.,Jabeen, T.,Sharma, S.,Yadav, S.,Kaur, P.,Kumar, P.,Srinivasan, A.,Singh, T.P.
Crystal Structure of a Novel Regulatory 40 kDa Mammary Gland Protein (MGP-40) secreted during Involution
J.Biol.Chem., 278:14451-14460, 2003

PubMed 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 beta/alpha domain structure with a triose-phosphate isomerase barrel conformation in the core and a small alpha+beta 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 Asp(115), Leu(119), and Asp(186) and in this case resulting in the loss of chitinase activity. The orientations of two Trp residues Trp(78) and Trp(331) in the beta 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.

PubMed: 12529329
DOI: 10.1074/jbc.M208967200

Experimental method

X-RAY DIFFRACTION (2.9 Å)