PDBsum entry: 1g1b

Lyase

PDB id: 1g1b

Contents

Protein chains

164 a.a. *

Ligands

PHB ×2

Waters ×250

* Residue conservation analysis

PDB id:

1g1b

Name:

Lyase

Title:

Chorismate lyase (wild-type) with bound product

Structure:

Chorismate lyase. Chain: a, b. Ec: 4.-.-.-

Source:

Escherichia coli. Organism_taxid: 562

Biol. unit:

Dimer (from PQS)

Resolution:

1.99Å R-factor: 0.196 R-free: 0.265

Authors:

D.T.Gallagher,M.Mayhew,M.J.Holden,K.J.Kim,A.Howard, V.L.Vilker

Key ref:

D.T.Gallagher et al. (2001). The crystal structure of chorismate lyase shows a new fold and a tightly retained product. Proteins, 44, 304-311. PubMed id: 11455603 DOI: 10.1002/prot.1095

Date:

11-Oct-00 Release date: 11-Apr-01

Protein chains

P26602  (UBIC_ECOLI) -  Chorismate--pyruvate lyase

Seq: 165 a.a.

Struc: 164 a.a.

Enzyme reactions

• Enzyme class: E.C.4.1.3.40 - Chorismate lyase.
• Reaction: Chorismate = 4-hydroxybenzoate + pyruvate

Chorismate = 4-hydroxybenzoate (Bound ligand (Het Group name = PHB) corresponds exactly) + pyruvate

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

 Gene Ontology (GO) functional annotation 

• Cellular component: cytoplasm (1 term)
• Biological process: ubiquinone biosynthetic process (1 term)
• Biochemical function: protein binding (3 terms)

reference

DOI no: 10.1002/prot.1095

Proteins 44:304-311 (2001)

PubMed id: 11455603

The crystal structure of chorismate lyase shows a new fold and a tightly retained product.

D.T.Gallagher, M.Mayhew, M.J.Holden, A.Howard, K.J.Kim, V.L.Vilker.

ABSTRACT

The enzyme chorismate lyase (CL) catalyzes the removal of pyruvate from chorismate to produce 4-hydroxy benzoate (4HB) for the ubiquinone pathway. In Escherichia coli, CL is monomeric, with 164 residues. We have determined the structure of the CL product complex by crystallographic heavy-atom methods and report the structure at 1.4-A resolution for a fully active double Cys-to-Ser mutant and at 2.0-A resolution for the wild-type. The fold involves a 6-stranded antiparallel beta-sheet with no spanning helices and novel connectivity. The product is bound internally, adjacent to the sheet, with its polar groups coordinated by two main-chain amides and by the buried side-chains of Arg 76 and Glu 155. The 4HB is completely sequestered from solvent in a largely hydrophobic environment behind two helix-turn-helix loops. The extensive product binding that is observed is consistent with biochemical measurements of slow product release and 10-fold stronger binding of product than substrate. Substrate binding and kinetically rate-limiting product release apparently require the rearrangement of these active-site-covering loops. Implications for the biological function of the high product binding are considered in light of the unique cellular role of 4HB, which is produced by cytoplasmic CL but is used by the membrane-bound enzyme 4HB octaprenyltransferase.

Selected figure(s)

Figure 4.
Figure 4. Ribbon diagram of the chorismate lyase (CL) structure. The enzymatic product 4HB and the chain of charged side-chains traversing it are shown as ball-and-stick, with dotted lines for hydrogen bonds. Ribbon colors progress from blue at the N-terminus to red at the C-terminus.

Figure 6.
Figure 6. Hypothetical model of flap motions involved in chorismate lyase (CL) product release. The model was made by global least-squares energy minimization of a series of 2-5-Å motions of 3-8 tip residues along a trajectory away from the active site. The crystal structure with 4HB-binding side-chains is shown in gold with 4HB in green. Pink, purple, and blue are used to show progressive opening of the flaps.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2001, 44, 304-311) copyright 2001.

Figures were selected by the author.

Author's comment

More recent reference dealing with dynamics/mechanism:
Smith N, Roitberg AE, Rivera E, Howard A, Holden MJ, Mayhew M, Kaistha S, Gallagher DT (2006). Structural analysis of ligand binding and catalysis in chorismate lyase. Arch. Biochem. Biophys., 445, 72-80. [PubMed: 16343413]