PDBsum entry 4k5m

Hydrolase/hydrolase inhibitor

PDB id: 4k5m

Contents

Protein chain

889 a.a.

Ligands

GOL ×3

1OV

Metals

_ZN

_MG ×2

Waters ×1147

PDB id:

4k5m

Name:

Hydrolase/hydrolase inhibitor

Title:

Phosphonic arginine mimetics as inhibitors of the m1 aminopeptidases from plasmodium falciparum

Structure:

M1 family aminopeptidase. Chain: a. Fragment: unp residues 195-1085. Synonym: pfa-m1. Engineered: yes. Mutation: yes

Source:

Plasmodium falciparum fcb1/columbia. Organism_taxid: 186763. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

1.75Å R-factor: 0.165 R-free: 0.207

Authors:

S.Mcgowan

Key ref:

K.Kannan Sivaraman et al. (2013). Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum. J Med Chem, 56, 5213-5217. PubMed id: 23713488 DOI: 10.1021/jm4005972

Date:

14-Apr-13 Release date: 12-Jun-13

Protein chain

O96935  (AMPN_PLAF7) -  Aminopeptidase N from Plasmodium falciparum (isolate 3D7)

Seq: 1085 a.a.

Struc: 889 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.4.11.- - ?????

DOI no: 10.1021/jm4005972

J Med Chem 56:5213-5217 (2013)

PubMed id: 23713488

Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum.

K.Kannan Sivaraman, A.Paiardini, M.Sieńczyk, C.Ruggeri, C.A.Oellig, J.P.Dalton, P.J.Scammells, M.Drag, S.McGowan.

ABSTRACT

The malaria parasite Plasmodium falciparum employs two metallo-aminopeptidases, PfA-M1 and PfA-M17, which are essential for parasite survival. Compounds that inhibit the activity of either enzyme represent leads for the development of new antimalarial drugs. Here we report the synthesis and structure-activity relationships of a small library of phosphonic acid arginine mimetics that probe the S1 pocket of both enzymes and map the necessary interactions that would be important for a dual inhibitor.