PDBsum entry 1c9d

Lyase

PDB id: 1c9d

Contents

Protein chains

264 a.a. *

387 a.a. *

Ligands

HF1

PLP

Metals

_NA

Waters ×188

* Residue conservation analysis

PDB id:

1c9d

Name:

Lyase

Title:

Crystal structure of the complex of bacterial tryptophan synthase with the transition state analogue inhibitor 4-(2-hydroxy-4- fluorophenylthio)-butylphosphonic acid

Structure:

Tryptophan synthase (alpha chain). Chain: a. Engineered: yes. Tryptophan synthase (beta chain). Chain: b. Engineered: yes

Source:

Salmonella typhimurium. Organism_taxid: 602. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Tetramer (from PDB file)

Resolution:

2.30Å R-factor: 0.211 R-free: 0.269

Authors:

E.Lolis,A.Sachpatzidis

Key ref:

A.Sachpatzidis et al. (1999). Crystallographic studies of phosphonate-based alpha-reaction transition-state analogues complexed to tryptophan synthase. Biochemistry, 38, 12665-12674. PubMed id: 10504236 DOI: 10.1021/bi9907734

Date:

02-Aug-99 Release date: 29-Dec-99

Protein chain

P00929  (TRPA_SALTY) -  Tryptophan synthase alpha chain from Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)

Seq: 268 a.a.

Struc: 264 a.a.

Protein chain

P0A2K1  (TRPB_SALTY) -  Tryptophan synthase beta chain from Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)

Seq: 397 a.a.

Struc: 387 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.4.2.1.20 - tryptophan synthase.
• Pathway: Tryptophan Biosynthesis
• Reaction: (1S,2R)-1-C-(indol-3-yl)glycerol 3-phosphate + L-serine = D-glyceraldehyde 3-phosphate + L-tryptophan + H2O
• Cofactor: Pyridoxal 5'-phosphate

Pyridoxal 5'-phosphate (Bound ligand (Het Group name = PLP) matches with 93.75% similarity)

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

reference

DOI no: 10.1021/bi9907734

Biochemistry 38:12665-12674 (1999)

PubMed id: 10504236

Crystallographic studies of phosphonate-based alpha-reaction transition-state analogues complexed to tryptophan synthase.

A.Sachpatzidis, C.Dealwis, J.B.Lubetsky, P.H.Liang, K.S.Anderson, E.Lolis.

ABSTRACT

In an effort to use a structure-based approach for the design of new herbicides, the crystal structures of complexes of tryptophan synthase with a series of phosphonate enzyme inhibitors were determined at 2.3 A or higher resolution. These inhibitors were designed to mimic the transition state formed during the alpha-reaction of the enzyme and, as expected, have affinities much greater than that of the natural substrate indole-3-glycerol phosphate or its nonhydrolyzable analogue indole propanol phosphate (IPP). These inhibitors are ortho-substituted arylthioalkylphosphonate derivatives that have an sp(3)-hybridized sulfur atom, designed to mimic the putative tetrahedral transition state at the C3 atom of the indole, and lack the C2 atom to allow for higher conformational flexibility. Overall, the inhibitors bind in a fashion similar to that of IPP. Glu-49 and Phe-212 are the two active site residues whose conformation changes upon inhibitor binding. A very short hydrogen bond between a phosphonate oxygen and the Ser-235 hydroxyl oxygen may be responsible for stabilization of the enzyme-inhibitor complexes. Implications for the mechanism of catalysis as well as directions for more potent inhibitors are discussed.