PDBsum entry 3qn7

Hydrolase/hydrolase inhibitor

PDB id: 3qn7

Contents

Protein chains

245 a.a.

16 a.a.

Ligands

ZBR

Waters ×132

PDB id:

3qn7

Name:

Hydrolase/hydrolase inhibitor

Title:

Potent and selective bicyclic peptide inhibitor (uk18) of human urokinase-type plasminogen activator(upa)

Structure:

Urokinase-type plasminogen activator. Chain: a. Fragment: catalytic domain, urokinase-type plasminogen activator chain b. Synonym: u-plasminogen activator, upa. Engineered: yes. Mutation: yes. Bicyclic peptide inhibitor. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: plau. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: human embryonic kidney cells (hek-293). Expression_system_cell: mammalian cells. Synthetic: yes.

Resolution:

1.90Å R-factor: 0.198 R-free: 0.252

Authors:

A.Angelini,L.Cendron,J.Touati,G.Winter,G.Zanotti,C.Heinis

Key ref:

A.Angelini et al. (2012). Bicyclic peptide inhibitor reveals large contact interface with a protease target. Acs Chem Biol, 7, 817-821. PubMed id: 22304751 DOI: 10.1021/cb200478t

Date:

08-Feb-11 Release date: 15-Feb-12

Protein chain

P00749  (UROK_HUMAN) -  Urokinase-type plasminogen activator from Homo sapiens

Seq: 431 a.a.

Struc: 245 a.a.*

Protein chain

No UniProt id for this chain

Struc: 16 a.a.

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

Enzyme reactions

• Enzyme class: Chain A: E.C.3.4.21.73 - u-plasminogen activator.
• Reaction: Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin.

DOI no: 10.1021/cb200478t

Acs Chem Biol 7:817-821 (2012)

PubMed id: 22304751

Bicyclic peptide inhibitor reveals large contact interface with a protease target.

A.Angelini, L.Cendron, S.Chen, J.Touati, G.Winter, G.Zanotti, C.Heinis.

ABSTRACT

From a large combinatorial library of chemically constrained bicyclic peptides we isolated a selective and potent (K(i) = 53 nM) inhibitor of human urokinase-type plasminogen activator (uPA) and crystallized the complex. This revealed an extended structure of the peptide with both peptide loops engaging the target to form a large interaction surface of 701 Å(2) with multiple hydrogen bonds and complementary charge interactions, explaining the high affinity and specificity of the inhibitor. The interface resembles that between two proteins and suggests that these constrained peptides have the potential to act as small protein mimics.