PDBsum entry: 1uvg

Serine proteinase inhibitor

PDB id: 1uvg

Contents

Protein chain

76 a.a. *

* Residue conservation analysis

PDB id:

1uvg

Name:

Serine proteinase inhibitor

Title:

Solution structure of the 15th domain of lekti

Structure:

Serine proteinase inhibitor kazal type 5. Chain: a. Fragment: lekti-domain15, residues 989-1064. Synonym: lympho-epithelial, kazal-type related inhibitor, lekti. Engineered: yes. Other_details: disulphide bonds between cys5 and cys40, between cys18 and cys37, between cys26 and cys58

Source:

Homo sapiens. Human. Organism_taxid: 9606. Tissue: vaginal epithel. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_variant: de3.

NMR struc:

31 models

Authors:

K.Vitzithum,P.Roesch,U.C.Marx

Key ref:

H.Tidow et al. (2004). The solution structure of a chimeric LEKTI domain reveals a chameleon sequence. Biochemistry, 43, 11238-11247. PubMed id: 15366933 DOI: 10.1021/bi0492399

Date:

20-Jan-04 Release date: 14-Apr-05

Protein chain

Q9NQ38  (ISK5_HUMAN) -  Serine protease inhibitor Kazal-type 5

Seq: 1064 a.a.

Struc: 76 a.a.

DOI no: 10.1021/bi0492399

Biochemistry 43:11238-11247 (2004)

PubMed id: 15366933

The solution structure of a chimeric LEKTI domain reveals a chameleon sequence.

H.Tidow, T.Lauber, K.Vitzithum, C.P.Sommerhoff, P.Rösch, U.C.Marx.

ABSTRACT

The conversion of an alpha-helical to a beta-strand conformation and the presence of chameleon sequences are fascinating from the perspective that such structural features are implicated in the induction of amyloid-related fatal diseases. In this study, we have determined the solution structure of a chimeric domain (Dom1PI) from the multidomain Kazal-type serine proteinase inhibitor LEKTI using multidimensional NMR spectroscopy. This chimeric protein was constructed to investigate the reasons for differences in the folds of the homologous LEKTI domains 1 and 6 [Lauber, T., et al. (2003) J. Mol. Biol. 328, 205-219]. In Dom1PI, two adjacent phenylalanine residues (F28 and F29) of domain 1 were substituted with proline and isoleucine, respectively, as found in the corresponding P4' and P5' positions of domain 6. The three-dimensional structure of Dom1PI is significantly different from the structure of domain 1 and closely resembles the structure of domain 6, despite the sequence being identical to that of domain 1 except for the two substituted phenylalanine residues and being only 31% identical to the sequence of domain 6. The mutation converted a short 3(10)-helix into an extended loop conformation and parts of the long COOH-terminal alpha-helix of domain 1 into a beta-hairpin structure. The latter conformational change occurs in a sequence stretch distinct from the region containing the substituted residues. Therefore, this switch from an alpha-helical structure to a beta-hairpin structure indicates a chameleon sequence of seven residues. We conclude that the secondary structure of Dom1PI is determined not only by the local protein sequence but also by nonlocal interactions.