5YHN
Solution structure of the LEKTI Domain 4
Summary for 5YHN
| Entry DOI | 10.2210/pdb5yhn/pdb |
| Descriptor | cDNA FLJ60407, highly similar to Serine protease inhibitor Kazal-type 5 (1 entity in total) |
| Functional Keywords | kazal, inhibitor, lekti, hydrolase inhibitor |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 8029.05 |
| Authors | Mok, Y.K.,Ramesh, K. (deposition date: 2017-09-29, release date: 2018-08-08, Last modification date: 2024-11-06) |
| Primary citation | 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 Cited by 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: 30017565DOI: 10.1016/j.str.2018.05.018 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
