5YHN

Solution structure of the LEKTI Domain 4

5YHN の概要

• エントリーDOI: 10.2210/pdb5yhn/pdb
• 分子名称: cDNA FLJ60407, highly similar to Serine protease inhibitor Kazal-type 5 (1 entity in total)
• 機能のキーワード: kazal, inhibitor, lekti, hydrolase inhibitor
• 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: 8029.05

構造登録者

Mok, Y.K.,Ramesh, K. (登録日: 2017-09-29, 公開日: 2018-08-08, 最終更新日: 2024-11-06)

主引用文献

Ramesh, K.,Lama, D.,Tan, K.W.,Nguyen, V.S.,Chew, F.T.,Verma, C.S.,Mok, Y.K.
Homologous Lympho-Epithelial Kazal-type Inhibitor Domains Delay Blood Coagulation by Inhibiting Factor X and XI with Differential Specificity.
Structure, 26:1178-1186.e3, 2018

PubMed Abstract: Despite being initially identified in the blood filtrate, LEKTI is a 15-domain Kazal-type inhibitor mostly known in the regulation of skin desquamation. In the current study, screening of serine proteases in blood coagulation cascade showed that LEKTI domain 4 has inhibitory activity toward only FXIa, whereas LEKTI domain 6 inhibits both FXIa and FXaB (bovine FXa). Nuclear magnetic resonance structural and dynamic experiments plus molecular dynamics simulation revealed that LEKTI domain 4 has enhanced backbone flexibility at the reactive-site loop. A model of the LEKTI-protease complex revealed that FXaB has a narrower S4 pocket compared with FXIa and hence prefers only small side-chain residues at the P4 position, such as Ala in LEKTI domain 6. Mutational studies combined with a molecular complex model suggest that both a more flexible reactive-site loop and a bulky residue at the P4 position make LEKTI domain 4 a weaker but highly selective inhibitor of FXIa.

PubMed: 30017565
DOI: 10.1016/j.str.2018.05.018

実験手法

SOLUTION NMR