PDBsum entry 2hg2

Oxidoreductase

PDB id: 2hg2

Contents

Protein chain

477 a.a. *

Ligands

SO4 ×2

Waters ×109

* Residue conservation analysis

PDB id:

2hg2

Name:

Oxidoreductase

Title:

Structure of lactaldehyde dehydrogenase

Structure:

Aldehyde dehydrogenase a. Chain: a. Synonym: lactaldehyde dehydrogenase, glycolaldehyde dehydrogenase, lad. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Gene: alda, ald. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.20Å R-factor: 0.221 R-free: 0.250

Authors:

L.Di Costanzo,G.A.Gomez,D.W.Christianson

Key ref:

L.Di Costanzo et al. (2007). Crystal Structure of Lactaldehyde Dehydrogenase from Escherichia coli and Inferences Regarding Substrate and Cofactor Specificity. J Mol Biol, 366, 481-493. PubMed id: 17173928 DOI: 10.1016/j.jmb.2006.11.023

Date:

26-Jun-06 Release date: 08-May-07

Protein chain

P25553  (ALDA_ECOLI) -  Lactaldehyde dehydrogenase from Escherichia coli (strain K12)

Seq: 479 a.a.

Struc: 477 a.a.

Enzyme reactions

• Enzyme class 1: E.C.1.2.1.21 - glycolaldehyde dehydrogenase.
• Reaction: glycolaldehyde + NAD⁺ + H2O = glycolate + NADH + 2 H⁺
• Enzyme class 2: E.C.1.2.1.22 - lactaldehyde dehydrogenase.
• Reaction: (S)-lactaldehyde + NAD⁺ + H2O = (S)-lactate + NADH + 2 H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

DOI no: 10.1016/j.jmb.2006.11.023

J Mol Biol 366:481-493 (2007)

PubMed id: 17173928

Crystal Structure of Lactaldehyde Dehydrogenase from Escherichia coli and Inferences Regarding Substrate and Cofactor Specificity.

L.Di Costanzo, G.A.Gomez, D.W.Christianson.

ABSTRACT

Aldehyde dehydrogenases catalyze the oxidation of aldehyde substrates to the corresponding carboxylic acids. Lactaldehyde dehydrogenase from Escherichia coli (aldA gene product, P25553) is an NAD(+)-dependent enzyme implicated in the metabolism of l-fucose and l-rhamnose. During the heterologous expression and purification of taxadiene synthase from the Pacific yew, lactaldehyde dehydrogenase from E. coli was identified as a minor (</=5%) side-product subsequent to its unexpected crystallization. Accordingly, we now report the serendipitous crystal structure determination of unliganded lactaldehyde dehydrogenase from E. coli determined by the technique of multiple isomorphous replacement using anomalous scattering at 2.2 A resolution. Additionally, we report the crystal structure of the ternary enzyme complex with products lactate and NADH at 2.1 A resolution, and the crystal structure of the enzyme complex with NADPH at 2.7 A resolution. The structure of the ternary complex reveals that the nicotinamide ring of the cofactor is disordered between two conformations: one with the ring positioned in the active site in the so-called hydrolysis conformation, and another with the ring extended out of the active site into the solvent region, designated the out conformation. This represents the first crystal structure of an aldehyde dehydrogenase-product complex. The active site pocket in which lactate binds is more constricted than that of medium-chain dehydrogenases such as the YdcW gene product of E. coli. The structure of the binary complex with NADPH reveals the first view of the structural basis of specificity for NADH: the negatively charged carboxylate group of E179 destabilizes the binding of the 2'-phosphate group of NADPH sterically and electrostatically, thereby accounting for the lack of enzyme activity with this cofactor.

Selected figure(s)

Figure 1.
Figure 1. Pathways of l-fucose and l-rhamnose metabolism in E. coli. Lactaldehyde dehydrogenase generates l-lactate, which is converted to pyruvate for entry into the central metabolic processes of the cell. Figure 1. Pathways of l-fucose and l-rhamnose metabolism in E. coli. Lactaldehyde dehydrogenase generates l-lactate, which is converted to pyruvate for entry into the central metabolic processes of the cell.

Figure 2.
Figure 2. The NAD^+-dependent oxidation of lactaldehyde to lactate catalyzed by lactaldehyde dehydrogenase. Figure 2. The NAD^+-dependent oxidation of lactaldehyde to lactate catalyzed by lactaldehyde dehydrogenase.

The above figures are reprinted from an Open Access publication published by Elsevier: J Mol Biol (2007, 366, 481-493) copyright 2007.

Figures were selected by an automated process.