PDBsum entry: 1ljy

Signaling protein

PDB id: 1ljy

Contents

Protein chain

361 a.a. *

Ligands

NAG-NDG

Waters ×48

* Residue conservation analysis

PDB id:

1ljy

Name:

Signaling protein

Title:

Crystal structure of a novel regulatory 40 kda mammary gland (mgp-40) secreted during involution

Structure:

Mgp-40. Chain: a

Source:

Capra hircus. Goat. Organism_taxid: 9925. Other_details: mammary gland secretory protein.

Resolution:

2.90Å R-factor: 0.181 R-free: 0.234

Authors:

A.K.Mohanty,G.Singh,M.Paramasivam,K.Saravanan,T.Jabeen,S.Sha S.Yadav,P.Kaur,P.Kumar,A.Srinivasan,T.P.Singh

Key ref:

A.K.Mohanty et al. (2003). Crystal structure of a novel regulatory 40-kDa mammary gland protein (MGP-40) secreted during involution. J Biol Chem, 278, 14451-14460. PubMed id: 12529329 DOI: 10.1074/jbc.M208967200

Date:

23-Apr-02 Release date: 18-Mar-03

Protein chain

Q8SPQ0  (CH3L1_CAPHI) -  Chitinase-3-like protein 1

Seq: 383 a.a.

Struc: 361 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (2 terms)
• Biological process: carbohydrate metabolic process (2 terms)
• Biochemical function: catalytic activity (5 terms)

DOI no: 10.1074/jbc.M208967200

J Biol Chem 278:14451-14460 (2003)

PubMed id: 12529329

Crystal structure of a novel regulatory 40-kDa mammary gland protein (MGP-40) secreted during involution.

A.K.Mohanty, G.Singh, M.Paramasivam, K.Saravanan, T.Jabeen, S.Sharma, S.Yadav, P.Kaur, P.Kumar, A.Srinivasan, T.P.Singh.

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.

Selected figure(s)

Figure 5.
Fig. 5. Linkage of the chain of the two units of GlcNAc (NAG). It is linked to 2 of the Asn39. Arg84 NH[2] forms a hydrogen bond network with O5 of the linked GlcNAc, as O 2 of Asn39 and O of Ile^40.

Figure 9.
Fig. 9. Comparison of the carbohydrate binding sites in the barrel of TIM domain. a, glucosamine (GCS) shown in red, fits well in YM1 (yellow), whereas there is a clash with the corresponding residues Phe^37, Trp78, Tyr185, and Trp331 in MGP-40 (green). b, similarly allosamidin (AMI) shown in red fits well in Chit1 (yellow), whereas AMI clashes with residues of MGP-40 (green).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 14451-14460) copyright 2003.

Figures were selected by an automated process.