9C54

Crystal structure of human PTPN2 catalytic domain

9C54 の概要

• エントリーDOI: 10.2210/pdb9c54/pdb
• 関連するPDBエントリー: 9C55 9C56
• 分子名称: Tyrosine-protein phosphatase non-receptor type 2 (2 entities in total)
• 機能のキーワード: phosphatase, apo, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36715.62

構造登録者

Bester, S.M.,Linwood, R.,Wu, W.-I.,Mou, T.-C. (登録日: 2024-06-05, 公開日: 2024-09-04, 最終更新日: 2024-09-25)

主引用文献

Bester, S.M.,Linwood, R.,Kataoka, R.,Wu, W.I.,Mou, T.C.
Enhancing the apo protein tyrosine phosphatase non-receptor type 2 crystal soaking strategy through inhibitor-accessible binding sites.
Acta Crystallogr.,Sect.F, 80:210-219, 2024

PubMed Abstract: Protein tyrosine phosphatase non-receptor type 2 (PTPN2) has recently been recognized as a promising target for cancer immunotherapy. Despite extensive structural and functional studies of other protein tyrosine phosphatases, there is limited structural understanding of PTPN2. Currently, there are only five published PTPN2 structures and none are truly unbound due to the presence of a mutation, an inhibitor or a loop (related to crystal packing) in the active site. In this report, a novel crystal packing is revealed that resulted in a true apo PTPN2 crystal structure with an unbound active site, allowing the active site to be observed in a native apo state for the first time. Key residues related to accommodation in the active site became identifiable upon comparison with previously published PTPN2 structures. Structures of PTPN2 in complex with an established PTPN1 active-site inhibitor and an allosteric inhibitor were achieved through soaking experiments using these apo PTPN2 crystals. The increased structural understanding of apo PTPN2 and the ability to soak in inhibitors will aid the development of future PTPN2 inhibitors.

PubMed: 39177701
DOI: 10.1107/S2053230X24007866

実験手法

X-RAY DIFFRACTION (2.05 Å)