PDBsum entry: 1t4b

Oxidoreductase

PDB id: 1t4b

Contents

Protein chains

367 a.a. *

Metals

_NA ×5

Waters ×967

* Residue conservation analysis

PDB id:

1t4b

Name:

Oxidoreductase

Title:

1.6 angstrom structure of esherichia coli aspartate- semialdehyde dehydrogenase.

Structure:

Aspartate-semialdehyde dehydrogenase. Chain: a, b. Synonym: asa dehydrogenase, asadh. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Gene: asd, hom, b3433, z4797, ecs4278, sf3456, s4307. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

1.60Å R-factor: 0.170 R-free: 0.199

Authors:

C.E.Nichols,B.Dhaliwal,M.Lockyer,A.R.Hawkins,D.K.Stammers

Key ref:

C.E.Nichols et al. (2004). High-resolution structures reveal details of domain closure and "half-of-sites-reactivity" in Escherichia coli aspartate beta-semialdehyde dehydrogenase. J Mol Biol, 341, 797-806. PubMed id: 15288787 DOI: 10.1016/j.jmb.2004.05.073

Date:

29-Apr-04 Release date: 13-Jul-04

Protein chains

P0A9Q9  (DHAS_ECOLI) -  Aspartate-semialdehyde dehydrogenase

Seq: 367 a.a.

Struc: 367 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.1.2.1.11 - Aspartate-semialdehyde dehydrogenase.
• Pathway: Lysine biosynthesis (early stages)
• Reaction: L-aspartate 4-semialdehyde + phosphate + NADP⁺ = L-4-aspartyl phosphate + NADPH

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

 Gene Ontology (GO) functional annotation 

• Cellular component: cytoplasm (1 term)
• Biological process: oxidation-reduction process (10 terms)
• Biochemical function: nucleotide binding (8 terms)

reference

DOI no: 10.1016/j.jmb.2004.05.073

J Mol Biol 341:797-806 (2004)

PubMed id: 15288787

High-resolution structures reveal details of domain closure and "half-of-sites-reactivity" in Escherichia coli aspartate beta-semialdehyde dehydrogenase.

C.E.Nichols, B.Dhaliwal, M.Lockyer, A.R.Hawkins, D.K.Stammers.

ABSTRACT

Two high-resolution structures have been determined for Eschericia coli aspartate beta-semialdehyde dehydrogenase (ecASADH), an enzyme of the aspartate biosynthetic pathway, which is a potential target for novel antimicrobial drugs. Both ASADH structures were of the open form and were refined to 1.95 A and 1.6 A resolution, allowing a more detailed comparison with the closed form of the enzyme than previously possible. A more complex scheme for domain closure is apparent with the subunit being split into two further sub-domains with relative motions about three hinge axes. Analysis of hinge data and torsion-angle difference plots is combined to allow the proposal of a detailed structural mechanism for ecASADH domain closure. Additionally, asymmetric distortions of individual subunits are identified, which form the basis for the previously reported "half-of-the-sites reactivity" (HOSR). A putative explanation of this arrangement is also presented, suggesting the HOSR system may provide a means for ecASADH to offset the energy required to remobilise flexible loops at the end of the reaction cycle, and hence avoid falling into an energy minimum.

Selected figure(s)

Figure 2.
Figure 2. Composite TAD plot (see Materials and Methods) with peaks labelled 1-3, La-Lc and S (see the text for an explanation of the symbols). (a) 2D sequence plot: X-axis, residue number; Y-axis, (mean TAD/2×SD).[2.] (d) 3D overlay of TAD sites from a onto cartoon format dimer structure. Spheres and bands indicate TAD peak sites (dark blue/purple, chain A; cyan/black, chain B). Structural representations were generated using VMD and all Figures prepared using Corel 11.

Figure 3.
Figure 3. (a) Cartoon format representation of ecASADH dimer C^a trace overlays, with the open form structure (form B) in green and the closed form structure (pdb1GL3) in red. For clarity, only the substrate analogue SMCS, cofactor NADPH and b-sheet regions of the protein are illustrated. (b) Modified TAD plot between chain A and chain B of the closed-form pdb1GL3 (see Materials and Methods). (c) 3D overlay of TAD sites from b onto the cartoon format representation of pdb1GL3 dimer, with the transformation axis to overlay subunit B onto subunit A marked as axis TA. Structural representations were generated using VMD and all Figures prepared using Corel 11.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 341, 797-806) copyright 2004.

Figures were selected by an automated process.