PDBsum entry 3lt2

Oxidoreductase

PDB id: 3lt2

Contents

Protein chains

287 a.a. *

Ligands

NAD ×2

FT3 ×2

Waters ×257

* Residue conservation analysis

PDB id:

3lt2

Name:

Oxidoreductase

Title:

Enoyl-acp reductase from plasmodium falciparum (pfenr) in complex with triclosan variant t3

Structure:

Enoyl-acp reductase. Chain: a, b. Fragment: residues 96-424. Engineered: yes

Source:

Plasmodium falciparum. Organism_taxid: 5833. Gene: fabi. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.50Å R-factor: 0.198 R-free: 0.248

Authors:

K.Maity,S.P.Bhargav,N.Surolia,A.Surolia,K.Suguna

Key ref:

K.Maity et al. (2010). X-ray crystallographic analysis of the complexes of enoyl acyl carrier protein reductase of Plasmodium falciparum with triclosan variants to elucidate the importance of different functional groups in enzyme inhibition. Iubmb Life, 62, 467-476. PubMed id: 20503440

Date:

14-Feb-10 Release date: 16-Jun-10

Protein chains

Q9BJJ9  (Q9BJJ9_PLAFA) -  Enoyl-ACP reductase (Fragment) from Plasmodium falciparum

Seq: 432 a.a.

Struc: 287 a.a.

Enzyme reactions

• Enzyme class: E.C.1.3.1.9 - enoyl-[acyl-carrier-protein] reductase (NADH).
• Reaction: a 2,3-saturated acyl-[ACP] + NAD⁺ = a (2E)-enoyl-[ACP] + NADH + H⁺

2,3-saturated acyl-[ACP] + NAD(+) (Bound ligand (Het Group name = NAD) corresponds exactly) = (2E)-enoyl-[ACP] + NADH + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

Iubmb Life 62:467-476 (2010)

PubMed id: 20503440

X-ray crystallographic analysis of the complexes of enoyl acyl carrier protein reductase of Plasmodium falciparum with triclosan variants to elucidate the importance of different functional groups in enzyme inhibition.

K.Maity, S.P.Bhargav, B.Sankaran, N.Surolia, A.Surolia, K.Suguna.

ABSTRACT

Triclosan, a well-known inhibitor of Enoyl Acyl Carrier Protein Reductase (ENR) from several pathogenic organisms, is a promising lead compound to design effective drugs. We have solved the X-ray crystal structures of Plasmodium falciparum ENR in complex with triclosan variants having different substituted and unsubstituted groups at different key functional locations. The structures revealed that 4 and 2' substituted compounds have more interactions with the protein, cofactor, and solvents when compared with triclosan. New water molecules were found to interact with some of these inhibitors. Substitution at the 2' position of triclosan caused the relocation of a conserved water molecule, leading to an additional hydrogen bond with the inhibitor. This observation can help in conserved water-based inhibitor design. 2' and 4' unsubstituted compounds showed a movement away from the hydrophobic pocket to compensate for the interactions made by the halogen groups of triclosan. This compound also makes additional interactions with the protein and cofactor which compensate for the lost interactions due to the unsubstitution at 2' and 4'. In cell culture, this inhibitor shows less potency, which indicates that the chlorines at 2' and 4' positions increase the ability of the inhibitor to cross multilayered membranes. This knowledge helps us to modify the different functional groups of triclosan to get more potent inhibitors.