PDBsum entry 1sfi

Hydrolase/hydrolase inhibitor

PDB id: 1sfi

Contents

Protein chains

223 a.a. *

14 a.a. *

Ligands

SO4 ×3

Metals

_CA

Waters ×376

* Residue conservation analysis

PDB id:

1sfi

Name:

Hydrolase/hydrolase inhibitor

Title:

High resolution structure of a potent, cyclic protease inhibitor from sunflower seeds

Structure:

Trypsin. Chain: a. Trypsin inhibitor 1. Chain: i. Synonym: sfti-1. Other_details: cyclic peptide

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Organ: pancreas. Helianthus annuus. Common sunflower. Organism_taxid: 4232. Strain: sunbred 246. Organ: seed.

Biol. unit:

Dimer (from PQS)

Resolution:

1.65Å R-factor: 0.175 R-free: 0.204

Authors:

S.Luckett,R.S.Garcia,J.J.Barker,A.V.Konarev,P.Shewry,A.R.Clarke, R.L.Brady

Key ref:

S.Luckett et al. (1999). High-resolution structure of a potent, cyclic proteinase inhibitor from sunflower seeds. J Mol Biol, 290, 525-533. PubMed id: 10390350 DOI: 10.1006/jmbi.1999.2891

Date:

16-Dec-98 Release date: 09-Jul-99

Protein chain

P00760  (TRY1_BOVIN) -  Serine protease 1 from Bos taurus

Seq: 246 a.a.

Struc: 223 a.a.

Protein chain

Q4GWU5  (SFTI1_HELAN) -  Trypsin inhibitor 1 from Helianthus annuus

Seq: 56 a.a.

Struc: 14 a.a.

Enzyme reactions

• Enzyme class: Chain A: E.C.3.4.21.4 - trypsin.
• Reaction: Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.

DOI no: 10.1006/jmbi.1999.2891

J Mol Biol 290:525-533 (1999)

PubMed id: 10390350

High-resolution structure of a potent, cyclic proteinase inhibitor from sunflower seeds.

S.Luckett, R.S.Garcia, J.J.Barker, A.V.Konarev, P.R.Shewry, A.R.Clarke, R.L.Brady.

ABSTRACT

Proteinaceous serine proteinase inhibitors are widespread throughout the plant kingdom where they play an important role in protection against pests and pathogens. Here, we describe the isolation and characterisation of a novel 14 amino acid residue cyclic peptide from sunflower seeds, which is a potent inhibitor of trypsin (Ki=100 pM). The crystal structure of this peptide in complex with bovine beta-trypsin shows both sequence and conformational similarity with the trypsin-reactive loop of the Bowman-Birk family of serine proteinase inhibitors. This inhibitor, however, is unique in being monofunctional, cyclic and far shorter (14 amino acid residues) than inhibitors belonging to this family (typically 60-70 amino acid residues). The high potency of this peptide is likely to arise from the considerable structural rigidity achieved through its cyclic nature which is further stabilised by a single internal disulphide bond. This study helps delineate the minimal unit required for effective peptide inhibitors of serine proteinases, and will assist in the further design of inhibitors to this widespread class of enzymes.

Selected figure(s)

Figure 4.
Figure 4. C a traces showing superimpositions of SFTI-1 (red) with the Mung bean inhibitor (Li et al., 1994) shown in blue, Adzuki bean inhibitor (Tsunogae et al., 1986) shown in yellow, and soy- bean inhibitor (Werner & Wemmer, 1992) shown in green. The P1 lysine residue is indicated.

Figure 5.
Figure 5. Stereoview showing the interactions of the active site loop of the inhibitor with bovine trypsin. Lys5-I projects into the S1 pocket of the enzyme, delineating speci- ficity for trypsin-like serine protein- ases. SFTI-1 residues are shown in yellow and ordered water mol- ecules in red.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 290, 525-533) copyright 1999.

Figures were selected by an automated process.