PDBsum entry 1eai

Serine proteinase

PDB id: 1eai

Contents

Protein chains

240 a.a. *

61 a.a. *

Waters ×146

* Residue conservation analysis

PDB id:

1eai

Name:

Serine proteinase

Title:

Complex of ascaris chymotrpsin/elastase inhibitor with porcine elastase

Structure:

Protein (elastase). Chain: a, b. Protein (chymotrypsin/elastase isoinhibitor 1). Chain: c, d

Source:

Sus scrofa. Pig. Organism_taxid: 9823. Organ: pancreas. Ascaris suum. Pig roundworm. Organism_taxid: 6253

Biol. unit:

Monomer (from PDB file)

Resolution:

2.40Å R-factor: 0.191

Authors:

K.Huang,N.C.J.Strynadka,V.D.Bernard,R.J.Peanasky,M.N.G.James

Key ref:

K.Huang et al. (1994). The molecular structure of the complex of Ascaris chymotrypsin/elastase inhibitor with porcine elastase. Structure, 2, 679-689. PubMed id: 7922044 DOI: 10.1016/S0969-2126(00)00068-X

Date:

25-Mar-99 Release date: 05-Apr-99

Protein chains

P00772  (CELA1_PIG) -  Chymotrypsin-like elastase family member 1 from Sus scrofa

Seq: 266 a.a.

Struc: 240 a.a.

Protein chains

P07851  (ICE1_ASCSU) -  Chymotrypsin/elastase isoinhibitor 1 from Ascaris suum

Seq: 63 a.a.

Struc: 61 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.3.4.21.36 - pancreatic elastase.
• Reaction: Hydrolysis of proteins, including elastin. Preferential cleavage: Ala-|-Xaa.

DOI no: 10.1016/S0969-2126(00)00068-X

Structure 2:679-689 (1994)

PubMed id: 7922044

The molecular structure of the complex of Ascaris chymotrypsin/elastase inhibitor with porcine elastase.

K.Huang, N.C.Strynadka, V.D.Bernard, R.J.Peanasky, M.N.James.

ABSTRACT

BACKGROUND: The intestinal parasitic worm, Ascaris suum, produces a variety of protein inhibitors that defend the organism against the host's proteinases. Eight different proteins from Ascaris suum have been identified as inhibitors of serine proteinases, targeting chymotrypsin, elastase and trypsin. These inhibitors share 30-40% sequence identity with one another, but have virtually no sequence identity with members of any of the other families of serine proteinase inhibitors. RESULTS: The crystal structure of the complex of porcine pancreatic elastase with a chymotrypsin/elastase inhibitor from Ascaris suum (the C/E-1 inhibitor) has been solved to 2.4 A resolution by the molecular replacement method. The C/E-1 inhibitor exhibits a novel folding motif. There are only two small beta-sheets and two single-turn 3(10)-helices in this inhibitor. Unlike the majority of proteins, the C/E-1 inhibitor does not have a hydrophobic core. The presence and unique topography of the five disulfide bridges suggests that they play important roles in maintaining the tertiary structure of the inhibitor. In addition, the side chains of several charged residues from electrostatic and hydrogen-bonding cascades, which also probably compensate for the lack of extensive secondary structures and a hydrophobic core. The reactive-site loop of this inhibitor displays a conformation that is characteristic of most serine proteinase inhibitors. CONCLUSIONS: The structure of the C/E-1 inhibitor confirms that inhibitors from Ascaris suum belong to a novel family of proteinase inhibitors. It also provides conclusive evidence for the correct disulfide bridge connections. The C/E-1 inhibitor probably acts by a common inhibitory mechanism proposed for other substrate-like protein inhibitors of serine proteinases. The unusual molecular scaffolding presents a challenge to current folding algorithms. Proteins like the C/E-1 inhibitor may provide a valuable model system to study how the primary sequence of a protein dictates its three-dimensional structure.

Selected figure(s)

Figure 4.
Figure 4. The salt bridge/hydrogen-bond network centered on Arg48 I. The side chain of Arg48 I, and the peptide nitrogen atoms of Gly6 I and Cys40 I are shown in blue. The side chain of Glu9 I, the side chain of Glu18 I and the peptide oxygen of Gly52 I are shown in red. Dashed lines represent hydrogen bonds or salt bridges within 3.2 å. Figure 4. The salt bridge/hydrogen-bond network centered on Arg48 I. The side chain of Arg48 I, and the peptide nitrogen atoms of Gly6 I and Cys40 I are shown in blue. The side chain of Glu9 I, the side chain of Glu18 I and the peptide oxygen of Gly52 I are shown in red. Dashed lines represent hydrogen bonds or salt bridges within 3.2 å.

Figure 7.
Figure 7. Superposition of residues P [3]to P [2]′ of the reactive-site loops from a selection of protein inhibitors of serine proteinases. The C/E-1 inhibitor is shown in green, bovine pancreatic trypsin inhibitor (BPTI) in yellow, ovomucoid inhibitor third domain from turkey (OMTKY3) in red, chymotrypsin inhibitor-1 from potato (PCI-1) in cyan, leech inhibitor eglin-c in purple and Bowman–Birk inhibitor from beans in pink. Figure 7. Superposition of residues P [3]to P [2]′ of the reactive-site loops from a selection of protein inhibitors of serine proteinases. The C/E-1 inhibitor is shown in green, bovine pancreatic trypsin inhibitor (BPTI) in yellow, ovomucoid inhibitor third domain from turkey (OMTKY3) in red, chymotrypsin inhibitor-1 from potato (PCI-1) in cyan, leech inhibitor eglin-c in purple and Bowman–Birk inhibitor from beans in pink.

The above figures are reprinted by permission from Cell Press: Structure (1994, 2, 679-689) copyright 1994.

Figures were selected by an automated process.