Crystal structure of breast regression protein 39 (BRP39), a signaling glycoprotein expressed during mammary gland apoptosis, at 2.6 Å resolution

Ashok K. Mohanty, Suman Choudhary, Jai K. Kaushik, Andrew J. Fisher

Research output: Contribution to journalArticlepeer-review

Abstract

Breast regression protein 39 (BRP39) is a 39 kDa protein that is a member of chitolectin class of glycosyl hydrolase family 18 (GH18). High expression levels of BRP39 have been detected in breast carcinoma. It helps in proliferation of cells during the progression of this disease and may act as a signaling factor. BRP39 may act as a potential candidate for rational structure-based drug design against breast carcinoma. In this study, we report the crystal structure of mouse recombinant BRP39 expressed in E. coli. The structure was solved by molecular replacement and refined to 2.6 Å resolution. The overall structure of BRP39 consisted of two globular domains: a large (β/α)8 triosephosphate isomerase (TIM) barrel domain and a small (α + β) domain. Three non-proline cis-peptides were detected in the sugar-binding cleft of BRP39, including Ser57-Phe58, Leu141-Tyr142, and Trp353-Ala354. The latter residues were conserved in other GH18 family members. It was notable that the conformation of critical Trp100 residue within the sugar-binding cleft was oriented away from the barrel. The side-chain conformation was found to be similar to that observed in chitinases, however, it was oriented into the barrel in other chitinase-like proteins (CLPs). The conformation of this critical residue may have significant implications in sugar binding. Further, two amino acid substitutions were observed in the sugar-binding groove of BRP39. The conserved Asn100 and Arg263 in Hcgp39 and other CLPs proteins (SPX-40 structures) were substituted by Lys101 and Lys264 in BRP39 which may have a significant impact on the sugar-binding properties.

Original languageEnglish (US)
Article number107737
JournalJournal of Structural Biology
Volume213
Issue number2
DOIs
StatePublished - Jun 2021

Keywords

  • Chitinase-like protein
  • Chitinases
  • Glycosyl hydrolases
  • Substrate
  • TIM barrel

ASJC Scopus subject areas

  • Structural Biology

Fingerprint

Dive into the research topics of 'Crystal structure of breast regression protein 39 (BRP39), a signaling glycoprotein expressed during mammary gland apoptosis, at 2.6 Å resolution'. Together they form a unique fingerprint.

Cite this