PDBsum entry 1t9e

Hydrolase/hydrolase inhibitor

PDB id: 1t9e

Contents

Protein chain

14 a.a.

PDB id:

1t9e

Name:

Hydrolase/hydrolase inhibitor

Title:

Nmr solution structure of a disulfide analogue of the cyclic sunflower trypsin inhibitor sfti-1

Structure:

Trypsin inhibitor 1. Chain: a. Synonym: sfti-1. Engineered: yes. Mutation: yes

Source:

Synthetic: yes. Helianthus annuus. Common sunflower. Organism_taxid: 4232. Other_details: the peptide was synthesized using standard solid phase peptide synthesis methods using boc chemistry. The peptide backbone was cyclicized in solution by addition of hbtu and diea which resulted in the formation of a peptide bond between d14 and g1. The sequence of the peptide is naturally found in helianthus

NMR struc:

20 models

Authors:

M.L.J.Korsinczky,R.J.Clark,D.J.Craik

Key ref:

M.L.Korsinczky et al. (2005). Disulfide bond mutagenesis and the structure and function of the head-to-tail macrocyclic trypsin inhibitor SFTI-1. Biochemistry, 44, 1145-1153. PubMed id: 15667208 DOI: 10.1021/bi048297r

Date:

16-May-04 Release date: 03-May-05

Protein chain

Q4GWU5  (SFTI1_HELAN) -  Trypsin inhibitor 1 from Helianthus annuus

Seq: 56 a.a.

Struc: 14 a.a.*

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

DOI no: 10.1021/bi048297r

Biochemistry 44:1145-1153 (2005)

PubMed id: 15667208

Disulfide bond mutagenesis and the structure and function of the head-to-tail macrocyclic trypsin inhibitor SFTI-1.

M.L.Korsinczky, R.J.Clark, D.J.Craik.

ABSTRACT

SFTI-1 is a novel 14 amino acid peptide comprised of a circular backbone constrained by three proline residues, a hydrogen-bond network, and a single disulfide bond. It is the smallest and most potent known Bowman-Birk trypsin inhibitor and the only one with a cyclic peptidic backbone. The solution structure of [ABA(3,11)]SFTI-1, a disulfide-deficient analogue of SFTI-1, has been determined by (1)H NMR spectroscopy. The lowest energy structures of native SFTI-1 and [ABA(3,11)]SFTI-1 are similar and superimpose with a root-mean-square deviation over the backbone and heavy atoms of 0.26 +/- 0.09 and 1.10 +/- 0.22 A, respectively. The disulfide bridge in SFTI-1 was found to be a minor determinant for the overall structure, but its removal resulted in a slightly weakened hydrogen-bonding network. To further investigate the role of the disulfide bridge, NMR chemical shifts for the backbone H(alpha) protons of two disulfide-deficient linear analogues of SFTI-1, [ABA(3,11)]SFTI-1[6,5] and [ABA(3,11)]SFTI-1[1,14] were measured. These correspond to analogues of the cleavage product of SFTI-1 and a putative biosynthetic precursor, respectively. In contrast with the cyclic peptide, it was found that the disulfide bridge is essential for maintaining the structure of these open-chain analogues. Overall, the hydrogen-bond network appears to be a crucial determinant of the structure of SFTI-1 analogues.