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.

乳房退化蛋白 39 (BRP39) 是一种 39 kDa 的蛋白质，是糖基水解酶家族 18 (GH18) 壳凝素类的成员。已在乳腺癌中检测到 BRP39 的高表达水平。它有助于在这种疾病的进展过程中细胞增殖，并可能充当信号因子。BRP39 可作为基于结构的合理抗乳腺癌药物设计的潜在候选者。在这项研究中，我们报告了在大肠杆菌中表达的小鼠重组 BRP39 的晶体结构。该结构通过分子置换解析并精炼至 2.6 Å 分辨率。BRP39 的整体结构由两个球状结构域组成：一个大的 (β/α) ₈磷酸丙糖异构酶 (TIM) 桶状结构域和一个小的 (α + β) 结构域。三非脯氨酸顺式在 BRP39 的糖结合裂隙中检测到 -肽，包括 Ser57-Phe58、Leu141-Tyr142 和 Trp353-Ala354。后一种残基在其他 GH18 家族成员中是保守的。值得注意的是，糖结合裂缝内关键 Trp100 残基的构象远离桶。发现侧链构象与在几丁质酶中观察到的相似，然而，它在其他几丁质酶样蛋白 (CLP) 中被定向到桶中。这个关键残基的构象可能对糖结合具有重要意义。此外，在 BRP39 的糖结合沟中观察到两个氨基酸取代。