PDBsum entry 2fqt

Lyase

PDB id: 2fqt

Contents

Protein chain

154 a.a. *

Ligands

SO4 ×2

H1D

Metals

_CO

Waters ×137

* Residue conservation analysis

PDB id:

2fqt

Name:

Lyase

Title:

Crystal structure of b.Subtilis luxs in complex with (2s)-2-amino-4- [(2r,3s)-2,3-dihydroxy-3-n-hydroxycarbamoyl-propylmercapto]butyric acid

Structure:

S-ribosylhomocysteine lyase. Chain: a. Synonym: autoinducer-2 production protein luxs, ai-2 synthesis protein. Engineered: yes

Source:

Bacillus subtilis. Organism_taxid: 1423. Gene: luxs. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PDB file)

Resolution:

1.79Å R-factor: 0.194 R-free: 0.226

Authors:

G.Shen,R.Rajan,J.Zhu,C.E.Bell,D.Pei

Key ref:

G.Shen et al. (2006). Design and synthesis of substrate and intermediate analogue inhibitors of S-ribosylhomocysteinase. J Med Chem, 49, 3003-3011. PubMed id: 16686542 DOI: 10.1021/jm060047g

Date:

18-Jan-06 Release date: 30-May-06

Protein chain

O34667  (LUXS_BACSU) -  S-ribosylhomocysteine lyase from Bacillus subtilis (strain 168)

Seq: 157 a.a.

Struc: 154 a.a.

Enzyme reactions

• Enzyme class: E.C.4.4.1.21 - S-ribosylhomocysteine lyase.
• Pathway: Autoinducer AI-2 Biosynthesis
• Reaction: S-(5-deoxy-D-ribos-5-yl)-L-homocysteine = (S)-4,5-dihydroxypentane-2,3- dione + L-homocysteine

S-(5-deoxy-D-ribos-5-yl)-L-homocysteine (Bound ligand (Het Group name = H1D) matches with 78.95% similarity) = (S)-4,5-dihydroxypentane-2,3- dione + L-homocysteine

• Cofactor: Fe(2+)

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

Added reference

DOI no: 10.1021/jm060047g

J Med Chem 49:3003-3011 (2006)

PubMed id: 16686542

Design and synthesis of substrate and intermediate analogue inhibitors of S-ribosylhomocysteinase.

G.Shen, R.Rajan, J.Zhu, C.E.Bell, D.Pei.

ABSTRACT

S-Ribosylhomocysteinase (LuxS) catalyzes the cleavage of the thioether linkage in S-ribosylhomocysteine (SRH) to produce homocysteine and 4,5-dihydroxy-2,3-pentanedione, the precursor of autoinducer 2. Inhibitors of LuxS should interfere with bacterial interspecies communication and potentially provide a novel class of antibacterial agents. LuxS utilizes a divalent metal ion as a Lewis acid during catalysis. In this work, a series of structural analogues of the substrate SRH and a 2-ketone intermediate were designed and synthesized. Kinetic studies indicate that the compounds act as reversible, competitive inhibitors against LuxS, with the most potent inhibitors having K(I) values in the submicromolar range. These represent the most potent LuxS inhibitors that have been reported to date. Cocrystal structures of LuxS bound with two of the inhibitors largely confirmed the design principles, i.e., the importance of both the homocysteine and ribose moieties in high-affinity binding to the LuxS active site.