PDBsum entry 1k7f

Lyase

PDB id: 1k7f

Contents

Protein chains

253 a.a. *

380 a.a. *

Ligands

IAV

PLP

Waters ×150

* Residue conservation analysis

PDB id:

1k7f

Name:

Lyase

Title:

Crystal structure of wild-type tryptophan synthase complexed with n- [1h-indol-3-yl-acetyl]valine acid

Structure:

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

Source:

Salmonella typhimurium. Organism_taxid: 602. Gene: trpa/trpb. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Tetramer (from PDB file)

Resolution:

1.90Å R-factor: 0.200 R-free: 0.251

Authors:

M.Weyand,I.Schlichting,A.Marabotti,A.Mozzarelli

Key ref:

M.Weyand et al. (2002). Crystal structures of a new class of allosteric effectors complexed to tryptophan synthase. J Biol Chem, 277, 10647-10652. PubMed id: 11756456 DOI: 10.1074/jbc.M111285200

Date:

19-Oct-01 Release date: 10-Jul-02

Protein chain

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

Seq: 268 a.a.

Struc: 253 a.a.

Protein chain

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

Seq: 397 a.a.

Struc: 380 a.a.

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

(1S,2R)-1-C-(indol-3-yl)glycerol 3-phosphate + L-serine = D-glyceraldehyde 3-phosphate + L-tryptophan + H2O (Bound ligand (Het Group name = IAV) matches with 52.17% similarity)

• 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: 10.1074/jbc.M111285200

J Biol Chem 277:10647-10652 (2002)

PubMed id: 11756456

Crystal structures of a new class of allosteric effectors complexed to tryptophan synthase.

M.Weyand, I.Schlichting, A.Marabotti, A.Mozzarelli.

ABSTRACT

Tryptophan synthase is a bifunctional alpha(2)beta(2) complex catalyzing the last two steps of l-tryptophan biosynthesis. The natural substrates of the alpha-subunit indole- 3-glycerolphosphate and glyceraldehyde-3-phosphate, and the substrate analogs indole-3-propanolphosphate and dl-alpha-glycerol-3-phosphate are allosteric effectors of the beta-subunit activity. It has been shown recently, that the indole-3-acetyl amino acids indole-3-acetylglycine and indole-3-acetyl-l-aspartic acid are both alpha-subunit inhibitors and beta-subunit allosteric effectors, whereas indole-3-acetyl-l-valine is only an alpha-subunit inhibitor (Marabotti, A., Cozzini, P., and Mozzarelli, A. (2000) Biochim. Biophys. Acta 1476, 287-299). The crystal structures of tryptophan synthase complexed with indole-3-acetylglycine and indole-3-acetyl-l-aspartic acid show that both ligands bind to the active site such that the carboxylate moiety is positioned similarly as the phosphate group of the natural substrates. As a consequence, the residues of the alpha-active site that interact with the ligands are the same as observed in the indole 3-glycerolphosphate-enzyme complex. Ligand binding leads to closure of loop alphaL6 of the alpha-subunit, a key structural element of intersubunit communication. This is in keeping with the allosteric role played by these compounds. The structure of the enzyme complex with indole-3-acetyl-l-valine is quite different. Due to the hydrophobic lateral chain, this molecule adopts a new orientation in the alpha-active site. In this case, closure of loop alphaL6 is no longer observed, in agreement with its functioning only as an inhibitor of the alpha-subunit reaction.

Selected figure(s)

Figure 1.
Fig. 1. 2mF[o] DF[c] electron density for the TRPSIAAA structures at the -active site. The density is shown at 1 -contouring for the IAAA molecule, Glu49, Asp60, Thr183, and for water molecules, which form hydrogen bonds with the -ligand. The hydrogen bonds of the enzymatic important amino acids Glu49 and Asp60 are shown as dashed lines (see Table II). The figure was prepared using "BOBSCRIPT" (40), "MOLSCRIPT" (41), and "RASTER3D" (42, 43). A, TRPSIAD structure. B, TRPSIAG structure. The second conformation of Glu49 is shown in orange. C, TRPSIAV structure.

Figure 2.
Fig. 2. Stereo plot of the structure superposition of TRPSIPP , TRPSIAD, and TRPSIAV. The C[ ]-atom trace is shown for TRPSIPP; the -subunit is colored in gray, loops L2 and L6 in cyan, and the -subunit in pink. The IPP, IAD, and IAV ligand C-atoms are colored in yellow, green, or orange, respectively. Nitrogen atoms are colored in blue, oxygen atoms are colored in red, and phosphate atoms are colored in magenta. The figure was prepared using MOLSCRIPT (41) and RASTER3D (42).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 10647-10652) copyright 2002.

Figures were selected by an automated process.