PDBsum entry: 1h0z

Serine proteinase inhibitor

PDB id: 1h0z

Contents

Protein chain

68 a.a. *

* Residue conservation analysis

PDB id:

1h0z

Name:

Serine proteinase inhibitor

Title:

Lekti domain six

Structure:

Serine protease inhibitor kazal-type 5, contains hemofiltrate peptide hf6478, hemofiltrate peptide hf7665. Chain: a. Fragment: lekti domain six (hf7665), residues 356-423. Synonym: hf7665, lympho-epithelial kazal-type related inhibitor, lekti. Other_details: disulfide linkage between cys a12 and cys a48, and between cys a26 and cys a45

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organ: blood. Cell: lympho epithelial cells

NMR struc:

21 models

Authors:

T.Lauber,P.Roesch,U.C.Marx

Key ref:

T.Lauber et al. (2003). Homologous proteins with different folds: the three-dimensional structures of domains 1 and 6 of the multiple Kazal-type inhibitor LEKTI. J Mol Biol, 328, 205-219. PubMed id: 12684009 DOI: 10.1016/S0022-2836(03)00245-6

Date:

01-Jul-02 Release date: 26-Jun-03

Protein chain

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

Seq: 1064 a.a.

Struc: 68 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1016/S0022-2836(03)00245-6

J Mol Biol 328:205-219 (2003)

PubMed id: 12684009

Homologous proteins with different folds: the three-dimensional structures of domains 1 and 6 of the multiple Kazal-type inhibitor LEKTI.

T.Lauber, A.Schulz, K.Schweimer, K.Adermann, U.C.Marx.

ABSTRACT

We have determined the solution structures of recombinant domain 1 and native domain 6 of the multi-domain Kazal-type serine proteinase inhibitor LEKTI using multi-dimensional NMR spectroscopy. While two of the 15 potential inhibitory LEKTI domains contain three disulfide bonds typical of Kazal-type inhibitors, the remaining 13 domains have only two of these disulfide bridges. Therefore, they may represent a novel type of serine proteinase inhibitor. The first and the sixth LEKTI domain, which have been isolated from human blood ultrafiltrate, belong to this group. In spite of sharing the same disulfide pattern and a sequence identity of about 35% from the first to the fourth cysteine, the two proteins show different structures in this region. The three-dimensional structure of domain 6 consists of two helices and a beta-hairpin structure, and closely resembles the three-dimensional fold of classical Kazal-type serine proteinase inhibitors including the inhibitory binding loop. Domain 6 has been shown to be an efficient, but non-permanent serine proteinase inhibitor. The backbone geometry of its canonical loop is not as well defined as the remaining structural elements, providing a possible explanation for its non-permanent inhibitory activity. We conclude that domain 6 belongs to a subfamily of classical Kazal-type inhibitors, as the third disulfide bond and a third beta-strand are missing. The three-dimensional structure of domain 1 shows three helices and a beta-hairpin, but the central part of the structure differs remarkably from that of domain 6. The sequence adopting hairpin structure in domain 6 exhibits helical conformation in domain 1, and none of the residues within the putative P3 to P3' stretch features backbone angles that resemble those of the canonical loop of known proteinase inhibitors. No proteinase has been found to be inhibited by domain 1. We conclude that domain 1 adopts a new protein fold and is no canonical serine proteinase inhibitor.

Selected figure(s)

Figure 3.
Figure 3. (a) and (c) Best-fit backbone superimposition of the 21 lowest overall energy structures of domain 6 (a) and domain1 (c) (generated with MOLMOL[63.]). Helical elements are displayed in red, b-sheet structure is colored in green. (b) and (d) Schematic drawing of a representative structure of domain 6 (b) and domain 1 (d), indicating regular secondary structural elements (same color code as in (a) and (c)). The heavy side-chain atoms of the P1 and P1' residues of domain 6 (Arg383 and Glu384) and the corresponding residues of domain 1 (Gln46 and Asp47) are shown (generated with MOLSCRIPT [65.] and Raster3D [66. and 67.]).

Figure 5.
Figure 5. Schematic drawings of the best-fit superimpositions of matching structural elements of domain 6 and BUSI IIA (2bus.PDB) (a) and of domains 1 and 6 (b). For BUSI IIA and domain 1 helical elements are displayed in orange, b-sheet structure is colored in cyan (for domain 6 same color code as in Figure 3).

The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 328, 205-219) copyright 2003.

Figures were selected by the author.