PDBsum entry: 1brm

Oxidoreductase

PDB-id: 1brm

Asymmetric unit

Contents

Description

Header details

Header records

References

PROCHECK

Protein chains

356 a.a. *

Waters ×303

* Residue conservation analysis

Tools

Clefts Calculation

Biological unit, dimer
- as defined in PDB file (see also PQS)

PDB id:

1brm

Name:

Oxidoreductase

Title:

Aspartate beta-semialdehyde dehydrogenase from escherichia coli

Structure:

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

Source:

Escherichia coli. Organism_taxid: 562. Gene: asd. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_cell_line: jm109.

Biological unit:

Homo-dimer (from PDB file)

UniProt:

Chains A, B, C: P0A9Q9 (DHAS_ECOLI)

Seq:

Struc:

Seq:

367 a.a.

Struc:

356 a.a.

Key:	PfamA domain
Secondary structure	CATH domain

Enzyme class:

E.C.1.2.1.11   [IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Reaction:

L-aspartate 4-semialdehyde + phosphate + NADP⁺ = L-4-aspartyl phosphate + NADPH (see diagram below)

Pathway:

Lysine biosynthesis (early stages)

Resolution:

2.50Å

R-factor:

0.225

R-free:

0.294

Authors:

A.T.Hadfield,G.Kryger,J.Ouyang,D.Ringe,G.A.Petsko,R.E.Viola

Key ref:

A.Hadfield et al. (1999). Structure of aspartate-beta-semialdehyde dehydrogenase from Escherichia coli, a key enzyme in the aspartate family of amino acid biosynthesis.. J Mol Biol, 289, 991. [PubMed id: 10369777] [DOI: 10.1006/jmbi.1999.2828]

Date:

24-Aug-98

Release date:

22-Jun-99

Quick_links

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Surface

Key reference

DOI no: 10.1006/jmbi.1999.2828

J Mol Biol 289:991 (1999)

PubMed id: 10369777

Structure of aspartate-beta-semialdehyde dehydrogenase from Escherichia coli, a key enzyme in the aspartate family of amino acid biosynthesis.

A.Hadfield, G.Kryger, J.Ouyang, G.A.Petsko, D.Ringe, R.Viola.

ABSTRACT

Aspartate beta-semialdehyde dehydrogenase (ASADH) lies at the first branch point in an essential aspartic biosynthetic pathway found in bacteria, fungi and the higher plants. Mutations in the asd gene encoding for ASADH that produce an inactive enzyme are lethal, which suggests that ASADH may be an effective target for antibacterial, herbicidal and fungicidal agents.We have solved the crystal structure of the Escherichia coli enzyme to 2.5 A resolution using single isomorphous replacement and 3-fold non-crystallographic symmetry. Each monomer has an N-terminal nucleotide-binding domain and a dimerisation domain. The presence of an essential cysteine locates the active site in a cleft between the two domains. The functional dimer has the appearance of a butterfly, with the NADP-binding domains forming the wings and the dimerisation domain forming the body.A histidine residue is identified as a likely acid/base catalyst in the enzymic reaction. Other amino acids implicated in the enzymic activity by mutagenesis are found in the active site region and define the substrate binding pocket.

Selected figure(s)

Figure 4.
Figure 4. Comparison of the aspartate-b-semialdehyde dehydrogenase and glyceraldehyde-3-phosphate dehydrogen- ase, which perform similar chemistry. (a) Structure-based sequence alignment of ASADH and GAPDH. Secondary struc- ture elements are represented by cylinders (a-helix) and arrows (b-strands), above the sequence for ASADH and below for GAPDH. The NAD(P)-binding fold fingerprint glycine residues and catalytic cysteine residues are boxed and similar residues are shaded (Barton, 1993). (b) Stereo views showing C a traces of the superimposed structures of B. stearothermo- philus GAPDH (grey) and E. coli ASADH (black). Numbering corresponds to ASADH sequence. (i) Dimerisation domain (ii) NADP-binding domain. The Figure was prepared using MOLSCRIPT (Kraulis, 1991).

Figure 5.
Figure 5. Cartoon representation of the active sites of GAPDH (grey) and ASADH (black). A sulphate (shown in grey) is observed in the GAPDH crystal structure and is believed to indicate part of the substrate binding site. The Figure was prepared using MOLSCRIPT (Kraulis, 1991).

The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 289, 991-0) copyright 1999.

Figures were selected by an automated process.