PDBsum entry 1n51

Hydrolase/hydrolase inhibitor

PDB id: 1n51

Contents

Protein chain

440 a.a. *

Ligands

01B-PRO-PRO-ALA-NH2

Metals

_MN ×3

Waters ×425

* Residue conservation analysis

PDB id:

1n51

Name:

Hydrolase/hydrolase inhibitor

Title:

Aminopeptidase p in complex with the inhibitor apstatin

Structure:

Xaa-pro aminopeptidase. Chain: a. Synonym: aminopeptidase p. Engineered: yes. Apstatin. Chain: b. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Gene: pepp. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Synthetic

Biol. unit:

Tetramer (from PDB file)

Resolution:

2.30Å R-factor: 0.179 R-free: 0.204

Authors:

S.C.Graham,M.J.Maher,M.H.Lee,W.H.Simmons,H.C.Freeman,J.M.Guss

Key ref:

S.C.Graham et al. (2004). Structure of Escherichia coli aminopeptidase P in complex with the inhibitor apstatin. Acta Crystallogr D Biol Crystallogr, 60, 1770-1779. PubMed id: 15388923 DOI: 10.1107/S0907444904018724

Date:

03-Nov-02 Release date: 16-Dec-03

Protein chain

P15034  (AMPP_ECOLI) -  Xaa-Pro aminopeptidase from Escherichia coli (strain K12)

Seq: 441 a.a.

Struc: 440 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.11.9 - Xaa-Pro aminopeptidase.
• Reaction: Release of any N-terminal amino acid, including proline, that is linked with proline, even from a dipeptide or tripeptide.
• Cofactor: Cobalt cation or Mn(2+)

DOI no: 10.1107/S0907444904018724

Acta Crystallogr D Biol Crystallogr 60:1770-1779 (2004)

PubMed id: 15388923

Structure of Escherichia coli aminopeptidase P in complex with the inhibitor apstatin.

S.C.Graham, M.J.Maher, W.H.Simmons, H.C.Freeman, J.M.Guss.

ABSTRACT

Aminopeptidase P (APPro) is a metalloprotease whose active site includes a dinuclear manganese(II) cluster. The enzyme cleaves the N-terminal residue from a polypeptide when the second residue is proline. A complex of Escherichia coli APPro (EcAPPro) with an inhibitor, apstatin [N-(2S,3R)-3-amino-2-hydroxy-4-phenyl-butanoyl-L-prolyl-L-prolyl-L-alaninamide], has been crystallized. Apstatin binds to the active site of EcAPPro with its N-terminal amino group coordinated to one of the two Mn(II) atoms at the metal centre. The apstatin hydroxyl group replaces a hydroxide ion which bridges the two metal atoms in the native enzyme. The first proline residue of apstatin lies in a small hydrophobic cleft. The structure of the apstatin-EcAPPro complex has been refined at 2.3 A resolution with residuals R = 0.179 and R(free) = 0.204. The structure of the complex illustrates how apstatin inhibits APPro and suggests how substrates may bind to the enzyme, but the basis of the proline-specificity remains elusive.

Selected figure(s)

Figure 4.
Figure 4 Stereoview of apstatin bound at the active site. The magenta spheres represent the MnII atoms. Only protein residues coordinating the metal atoms or forming hydrogen bonds with apstatin are shown. The `omit' F[o] - F[c] electron-density difference map calculated before apstatin was included in the model is contoured at 3 [168][sigma] .

Figure 6.
Figure 6 Two-dimensional schematic diagram showing the interactions between apstatin and EcAPPro. Hydrogen bonds (green dashed lines), inhibitor-metal ligand interactions (purple sticks) and hydrophobic interactions (red combs) a

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2004, 60, 1770-1779) copyright 2004.

Figures were selected by the author.