PDBsum entry 1fcj

Lyase

PDB id: 1fcj

Contents

Protein chains

302 a.a. *

Ligands

SO4 ×4

PLP ×4

Metals

_CL ×4

Waters ×1118

* Residue conservation analysis

PDB id:

1fcj

Name:

Lyase

Title:

Crystal structure of oass complexed with chloride and sulfate

Structure:

O-acetylserine sulfhydrylase. Chain: a, b, c, d. Synonym: cysteine synthase a, o-acetylserine (thiol)-lyase a, csase a. Ec: 4.2.99.8

Source:

Salmonella typhimurium. Organism_taxid: 602

Biol. unit:

Dimer (from PQS)

Resolution:

2.00Å R-factor: 0.200 R-free: 0.246

Authors:

P.Burkhard,C.Tai,J.N.Jansonius,P.F.Cook

Key ref:

P.Burkhard et al. (2000). Identification of an allosteric anion-binding site on O-acetylserine sulfhydrylase: structure of the enzyme with chloride bound. J Mol Biol, 303, 279-286. PubMed id: 11023792 DOI: 10.1006/jmbi.2000.4109

Date:

18-Jul-00 Release date: 18-Oct-00

Protein chains

P0A1E3  (CYSK_SALTY) -  Cysteine synthase A from Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)

Seq: 323 a.a.

Struc: 302 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.2.5.1.47 - cysteine synthase.
• Reaction: O-acetyl-L-serine + hydrogen sulfide = L-cysteine + acetate
• 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: 10.1006/jmbi.2000.4109

J Mol Biol 303:279-286 (2000)

PubMed id: 11023792

Identification of an allosteric anion-binding site on O-acetylserine sulfhydrylase: structure of the enzyme with chloride bound.

P.Burkhard, C.H.Tai, J.N.Jansonius, P.F.Cook.

ABSTRACT

A new crystal structure of O-acetylserine sulfhydrylase (OASS) has been solved with chloride bound at an allosteric site and sulfate bound at the active site. The bound anions result in a new "inhibited" conformation, that differs from the "open" native or "closed" external aldimine conformations. The allosteric site is located at the OASS dimer interface. The new inhibited structure involves a change in the position of the "moveable domain" (residues 87-131) to a location that differs from that in the open or closed forms. Formation of the external aldimine with substrate is stabilized by interaction of the alpha-carboxyl group of the substrate with a substrate-binding loop that is part of the moveable domain. The inhibited conformation prevents the substrate-binding loop from interacting with the alpha-carboxyl group, and hinders formation of the external Schiff base and thus subsequent chemistry. Chloride may be an analog of sulfide, the physiological inhibitor. Finally, these results suggest that OASS represents a new class of PLP-dependent enzymes that is regulated by small anions.

Selected figure(s)

Figure 2.
Figure 2. Stereo representation of the conformational changes occurring upon sulfate and chloride binding to OASS. The open conformation is depicted in cyan, the inhibited conformation is depicted in magenta, the moveable domain is shown with schematic drawings of the a-helices and b-sheets. Binding of chloride in the allosteric site causes a peptide flip of Pro36, which replaces the side-chain of Cys42, which then in turn pushes the side-chain of Tyr78 to the right. This new conformation of Tyr78 pushes Leu106 upwards and causes the moveable domain to undergo a large conformational change into the inhibited conformation.

Figure 3.
Figure 3. Overlay of the open (cyan), the closed (yellow) and the inhibited (magenta) conformations of OASS in stereo representation. The moveable domain is shown as a cylinder (a-helix) and arrow (b-strand) diagram. The pyridoxal 5'-phosphate (PLP) cofactor of the K41A mutant structure in external aldimine linkage with methionine is shown in ball and stick mode. While the C-terminal domain remains virtually unchanged, parts of the N-terminal domain, the moveable domain, undergo a substantial conformational change and switch from the open conformation either to the closed conformation (external aldimine) or to the inhibited conformation (sulfate/chloride). The Figure was produced with the programs MOLSCRIPT [Kraulis 1991] and Raster3D [Merritt and Bacon 1997].

The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 303, 279-286) copyright 2000.

Figures were selected by the author.