PDBsum entry: 2gyy

Oxidoreductase

PDB id: 2gyy

Contents

Protein chains

352 a.a. *

Waters ×1003

* Residue conservation analysis

PDB id:

2gyy

Name:

Oxidoreductase

Title:

Structure of aspartate semialdehyde dehydrogenase (asadh) fr streptococcus pneumoniae

Structure:

Aspartate beta-semialdehyde dehydrogenase. Chain: a, b, c, d. Engineered: yes

Source:

Streptococcus pneumoniae. Organism_taxid: 1313. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PQS)

Resolution:

2.10Å R-factor: 0.180 R-free: 0.221

Authors:

C.R.Faehnle,J.Le Coq,X.Liu,R.E.Viola

Key ref:

C.R.Faehnle et al. (2006). Examination of key intermediates in the catalytic cycle of aspartate-beta-semialdehyde dehydrogenase from a gram-positive infectious bacteria. J Biol Chem, 281, 31031-31040. PubMed id: 16895909 DOI: 10.1074/jbc.M605926200

Date:

10-May-06 Release date: 15-Aug-06

Protein chains

Q97R26  (Q97R26_STRPN) -  Aspartate-semialdehyde dehydrogenase

Seq: 358 a.a.

Struc: 352 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 (7 terms)
• Biochemical function: binding (9 terms)

reference

DOI no: 10.1074/jbc.M605926200

J Biol Chem 281:31031-31040 (2006)

PubMed id: 16895909

Examination of key intermediates in the catalytic cycle of aspartate-beta-semialdehyde dehydrogenase from a gram-positive infectious bacteria.

C.R.Faehnle, J.Le Coq, X.Liu, R.E.Viola.

ABSTRACT

Aspartate-beta-semialdehyde dehydrogenase (ASADH) catalyzes a critical branch point transformation in amino acid bio-synthesis. The products of the aspartate pathway are essential in microorganisms, and this entire pathway is absent in mammals, making this enzyme an attractive target for antibiotic development. The first structure of an ASADH from a Gram-positive bacterium, Streptococcus pneumoniae, has now been determined. The overall structure of the apoenzyme has a similar fold to those of the Gram-negative and archaeal ASADHs but contains some interesting structural variations that can be exploited for inhibitor design. Binding of the coenzyme NADP, as well as a truncated nucleotide analogue, into an alternative conformation from that observed in Gram-negative ASADHs causes an enzyme domain closure that precedes catalysis. The covalent acyl-enzyme intermediate was trapped by soaking the substrate into crystals of the coenzyme complex, and the structure of this elusive intermediate provides detailed insights into the catalytic mechanism.

Selected figure(s)

Figure 2.
FIGURE 2. NADP-induced domain closure in spASADH. Binding of NADP induces an 8° rotation of the N-terminal Rossmann fold toward the C-terminal dimerization domain. A, ribbon representation of spASADH domain closure induced by the binding of NADP. Shown is the opened form of spASADH with the moving domain (red), hinge-bending residues (green), and fixed domain (blue) highlighted. The hinge-bending axis is shown as black spheres. B, overlay of the opened form of spASADH (colored as in A) with the closed form (yellow). NADP is shown as modeled in the spASADH-NADP complex (white sticks). C, plot of C- backbone displacement in the opened to closed transition versus amino acid residue (moving residues, red; hinge residues, green; fixed residues, blue).

Figure 3.
FIGURE 3. Interactions between ASADH and NADP. A, NADP (yellow sticks) forms several interactions with spASADH in the closed form (green sticks), including electrostatic and hydrogen bonding interactions (...) and cation- interactions with the adenine ring ( ). An overlay of the opened form structure (white sticks) allows visualization of the side chain movements that take place to accommodate NADP binding. B, in contrast, the adenine ring of NADP occupies a completely different binding pocket in ecASADH (11), whereas the positions of the 2'-phosphate group and the nicotinamide ring are maintained.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 31031-31040) copyright 2006.

Figures were selected by an automated process.