PDBsum entry 1ljy

Go to PDB code: 
protein ligands links
Signaling protein PDB id
Protein chain
361 a.a. *
Waters ×48
* Residue conservation analysis
PDB id:
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.
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
23-Apr-02     Release date:   18-Mar-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q8SPQ0  (CH3L1_CAPHI) -  Chitinase-3-like protein 1
383 a.a.
361 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 7 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   5 terms 
  Biological process     cellular response to tumor necrosis factor   16 terms 
  Biochemical function     carbohydrate binding     4 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.
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.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20701447 A.B.Mathiasen, K.M.Henningsen, M.J.Harutyunyan, N.D.Mygind, and J.Kastrup (2010).
YKL-40: a new biomarker in cardiovascular disease?
  Biomark Med, 4, 591-600.  
19210126 F.Mannello, V.Medda, and G.A.Tonti (2009).
Protein profile analysis of the breast microenvironment to differentiate healthy women from breast cancer patients.
  Expert Rev Proteomics, 6, 43-60.  
19792974 J.S.Johansen, N.A.Schultz, and B.V.Jensen (2009).
Plasma YKL-40: a potential new cancer biomarker?
  Future Oncol, 5, 1065-1082.  
19307719 P.Sharma, N.Singh, M.Sinha, S.Sharma, M.Perbandt, C.Betzel, P.Kaur, A.Srinivasan, and T.P.Singh (2009).
Tryptophan as a three-way switch in regulating the function of the secretory signalling glycoprotein (SPS-40) from mammary glands: structure of SPS-40 complexed with 2-methylpentane-2,4-diol at 1.6 A resolution.
  Acta Crystallogr D Biol Crystallogr, 65, 375-378.
PDB code: 2pi6
18157633 A.Roslind, A.S.Knoop, M.B.Jensen, J.S.Johansen, D.L.Nielsen, P.A.Price, and E.Balslev (2008).
YKL-40 protein expression is not a prognostic marker in patients with primary breast cancer.
  Breast Cancer Res Treat, 112, 275-285.  
  17401190 A.S.Ethayathulla, D.B.Srivastava, J.Kumar, K.Saravanan, S.Bilgrami, S.Sharma, P.Kaur, A.Srinivasan, and T.P.Singh (2007).
Structure of the buffalo secretory signalling glycoprotein at 2.8 A resolution.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 258-265.
PDB code: 2o9o
17608806 F.Badariotti, C.Lelong, M.P.Dubos, and P.Favrel (2007).
Characterization of chitinase-like proteins (Cg-Clp1 and Cg-Clp2) involved in immune defence of the mollusc Crassostrea gigas.
  FEBS J, 274, 3646-3654.  
17372347 J.Kumar, A.S.Ethayathulla, D.B.Srivastava, N.Singh, S.Sharma, P.Kaur, A.Srinivasan, and T.P.Singh (2007).
Carbohydrate-binding properties of goat secretory glycoprotein (SPG-40) and its functional implications: structures of the native glycoprotein and its four complexes with chitin-like oligosaccharides.
  Acta Crystallogr D Biol Crystallogr, 63, 437-446.
PDB codes: 2dsz 2dt0 2dt1 2dt2 2dt3
17227236 J.S.Johansen, B.V.Jensen, A.Roslind, and P.A.Price (2007).
Is YKL-40 a new therapeutic target in cancer?
  Expert Opin Ther Targets, 11, 219-234.  
17565739 W.Qin, W.Zhu, L.Schlatter, R.Miick, T.S.Loy, U.Atasoy, J.E.Hewett, and E.R.Sauter (2007).
Increased expression of the inflammatory protein YKL-40 in precancers of the breast.
  Int J Cancer, 121, 1536-1542.  
17543889 Zaheer-ul-Haq, P.Dalal, N.N.Aronson, and J.D.Madura (2007).
Family 18 chitolectins: comparison of MGP40 and HUMGP39.
  Biochem Biophys Res Commun, 359, 221-226.  
16929095 J.Kumar, A.S.Ethayathulla, D.B.Srivastava, S.Sharma, S.B.Singh, A.Srinivasan, M.P.Yadav, and T.P.Singh (2006).
Structure of a bovine secretory signalling glycoprotein (SPC-40) at 2.1 Angstrom resolution.
  Acta Crystallogr D Biol Crystallogr, 62, 953-963.
PDB code: 2esc
15771622 N.Junker, J.S.Johansen, L.T.Hansen, E.L.Lund, and P.E.Kristjansen (2005).
Regulation of YKL-40 expression during genotoxic or microenvironmental stress in human glioblastoma cells.
  Cancer Sci, 96, 183-190.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.