PDBsum entry: 2b7o

Transferase

PDB id: 2b7o

Contents

Protein chains

451 a.a. *

Ligands

SO4 ×2

PEP ×2

CE1

Metals

_MN ×2

Waters ×336

* Residue conservation analysis

PDB id:

2b7o

Name:

Transferase

Title:

The structure of 3-deoxy-d-arabino-heptulosonate 7-phosphate from mycobacterium tuberculosis

Structure:

3-deoxy-d-arabino-heptulosonate 7-phosphate synth chain: a, b. Synonym: dah7ps, dahp synthetase, phenylalanine-repressible engineered: yes

Source:

Mycobacterium tuberculosis. Organism_taxid: 83332. Strain: h37rv. Gene: rv2178c. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.30Å R-factor: 0.190 R-free: 0.224

Authors:

C.J.Webby,H.M.Baker,J.S.Lott,E.N.Baker,E.J.Parker,Mycobacter Tuberculosis Structural Proteomics Project (Xmtb)

Key ref:

C.J.Webby et al. (2005). The structure of 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis reveals a common catalytic scaffold and ancestry for type I and type II enzymes. J Mol Biol, 354, 927-939. PubMed id: 16288916 DOI: 10.1016/j.jmb.2005.09.093

Date:

05-Oct-05 Release date: 18-Oct-05

Protein chains

O53512  (O53512_MYCTU) -  Probable 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase AroG (DAHP synthetase, phenylalanine-repressible)

Seq: 462 a.a.

Struc: 451 a.a.

Enzyme reactions

• Enzyme class: E.C.2.5.1.54 - 3-deoxy-7-phosphoheptulonate synthase.
• Pathway: Shikimate and Chorismate Biosynthesis
• Reaction: Phosphoenolpyruvate + D-erythrose 4-phosphate + H₂O = 3-deoxy-D- arabino-hept-2-ulosonate 7-phosphate + phosphate

Phosphoenolpyruvate (Bound ligand (Het Group name = PEP) corresponds exactly) + D-erythrose 4-phosphate + H(2)O = 3-deoxy-D- arabino-hept-2-ulosonate 7-phosphate + phosphate

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

 Gene Ontology (GO) functional annotation 

• Cellular component: plasma membrane (2 terms)
• Biological process: growth (5 terms)
• Biochemical function: protein binding (5 terms)

reference

DOI no: 10.1016/j.jmb.2005.09.093

J Mol Biol 354:927-939 (2005)

PubMed id: 16288916

The structure of 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis reveals a common catalytic scaffold and ancestry for type I and type II enzymes.

C.J.Webby, H.M.Baker, J.S.Lott, E.N.Baker, E.J.Parker.

ABSTRACT

The shikimate pathway, responsible for the biosynthesis of aromatic compounds, is essential for the growth of Mycobacterium tuberculosis and is a potential target for the design of new anti-tuberculosis drugs. The first step of this pathway is catalyzed by 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS). The DAH7PSs have been classified into two apparently unrelated types and, whereas structural data have been obtained for the type I DAH7PSs, no structural information is available for their type II counterparts. The type II DAH7PS from M.tuberculosis has been expressed in Escherichia coli, purified, functionally characterized and crystallized. It is found to be metal ion-dependent and subject to feedback inhibition by phenylalanine, tryptophan, tyrosine and chorismate, with a significant synergistic effect when tryptophan is used in combination with phenylalanine. The crystal structure of M.tuberculosis DAH7PS has been determined by single-wavelength anomalous diffraction and refined at 2.3A in complex with substrate phosphoenolpyruvate and Mn(2+). The structure reveals a tightly associated dimer of (beta/alpha)(8) TIM barrels. The monomer fold, the arrangement of key residues in the active site, and the binding modes of PEP and Mn(2+), all match those of the type I enzymes, and indicate a common ancestry for the type I and type II DAH7PSs, despite their minimal sequence identity. In contrast, the structural elements that decorate the core (beta/alpha)(8) fold differ from those in the type I enzymes, consistent with their different regulatory and oligomeric properties.

Selected figure(s)

Figure 2.
Figure 2. Active site of Mt-DAH7PS. (a) Stereo view showing the interactions with the manganese ion (magenta sphere), the PEP substrate (yellow and orange stick model) and the sulfate ion (green) that marks the likely position of the phosphate group of the E4P substrate, which is expected to fill the space between here and the metal site. Water molecules are shown as small red spheres. Metal-ligand bonds are shown with thin black lines, and hydrogen bonds with broken lines. Key residues that contribute to metal, PEP or sulfate binding are labeled. Cys440 can form a disulfide bond with the metal ligand Cys87, explaining the inactivation of the enzyme under oxidizing conditions. The invariant Glu248 would sit directly above the PEP C3 atom in this view, but has been removed for clarity. (b) Stereo view of the electron density for the PEP substrate, from a bias-removed "omit" map, contoured at 3s. The side-chains of Glu248 and Trp280 approach to within vert, similar 3 Å from the methylene carbon atom (C3) of PEP.

Figure 4.
Figure 4. Comparison of subunit structure of DAH7PS enzymes. The core (b/a)[8]-barrel common to all DAH7PSs is shown in blue. N-terminal extensions or domains are shown in red and other protrusions from the barrel are in yellow. The structures shown are for (a) Mt-DAH7PS, (b) Pf-DAH7PS, (c) Ec-DAH7PS, and (d) Tm-DAH7PS.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 354, 927-939) copyright 2005.

Figures were selected by the author.