PDBsum entry 1dpj

Hydrolase/hydrolase inhibitor

PDB id: 1dpj

Contents

Protein chains

329 a.a. *

29 a.a. *

Ligands

NAG-NAG-BMA-MAN-MAN-BMA-MAN-MAN-MAN

NAG

SO4 ×4

Waters ×372

* Residue conservation analysis

PDB id:

1dpj

Name:

Hydrolase/hydrolase inhibitor

Title:

The structure of proteinase a complexed with ia3 peptide inhibitor

Structure:

Proteinase a. Chain: a. Synonym: aspartate protease. Proteinase inhibitor ia3 peptide. Chain: b. Synonym: ia3. Engineered: yes

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Tetramer (from PQS)

Resolution:

1.80Å R-factor: 0.192 R-free: 0.213

Authors:

M.Li,H.L.Phylip,W.E.Lees,J.R.Winther,B.M.Dunn,A.Wlodawer,J.Kay, A.Guschina

Key ref:

M.Li et al. (2000). The aspartic proteinase from Saccharomyces cerevisiae folds its own inhibitor into a helix. Nat Struct Biol, 7, 113-117. PubMed id: 10655612 DOI: 10.1038/72378

Date:

27-Dec-99 Release date: 03-May-00

Protein chain

P07267  (CARP_YEAST) -  Saccharopepsin from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 405 a.a.

Struc: 329 a.a.

Protein chain

P01094  (IPA3_YEAST) -  Protease A inhibitor 3 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 68 a.a.

Struc: 29 a.a.

Enzyme reactions

• Enzyme class: Chain A: E.C.3.4.23.25 - saccharopepsin.
• Reaction: Hydrolysis of proteins with broad specificity for peptide bonds. Cleaves -Leu-Leu-|-Val-Tyr- bond in a synthetic substrate. Does not act on esters of Tyr or Arg.

DOI no: 10.1038/72378

Nat Struct Biol 7:113-117 (2000)

PubMed id: 10655612

The aspartic proteinase from Saccharomyces cerevisiae folds its own inhibitor into a helix.

M.Li, L.H.Phylip, W.E.Lees, J.R.Winther, B.M.Dunn, A.Wlodawer, J.Kay, A.Gustchina.

ABSTRACT

Aspartic proteinase A from yeast is specifically and potently inhibited by a small protein called IA3 from Saccharomyces cerevisiae. Although this inhibitor consists of 68 residues, we show that the inhibitory activity resides within the N-terminal half of the molecule. Structures solved at 2.2 and 1.8 A, respectively, for complexes of proteinase A with full-length IA3 and with a truncated form consisting only of residues 2-34, reveal an unprecedented mode of inhibitor-enzyme interactions. Neither form of the free inhibitor has detectable intrinsic secondary structure in solution. However, upon contact with the enzyme, residues 2-32 become ordered and adopt a near-perfect alpha-helical conformation. Thus, the proteinase acts as a folding template, stabilizing the helical conformation in the inhibitor, which results in the potent and specific blockage of the proteolytic activity.

Selected figure(s)

Figure 1.
Figure 1. Schematic diagram of the structure of proteinase A. Ribbon representation showing the tracing of the main chain of proteinase A (green) with the oligosaccharide attached to Asn 67 shown in mauve, together with the visible fragment of the inhibitor IA[3] (gold). Side chains of the active site residues Asp 32 and Asp 215 are shown in red.

Figure 3.
Figure 3. Interactions in the vicinity of the active site of proteinase A. Proteinase A (green, with the active site aspartates red) complexed to IA[3] (yellow with orange side chains) is superimposed on progastricsin (purple). Water molecules in the proteinase A complex are blue, and hydrogen bonds are marked as thin lines.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2000, 7, 113-117) copyright 2000.

Figures were selected by an automated process.