PDBsum entry 2o4c

Oxidoreductase

PDB id: 2o4c

Contents

Protein chains

380 a.a. *

Ligands

PO4

NAD ×2

TLA

GOL

Waters ×167

* Residue conservation analysis

PDB id:

2o4c

Name:

Oxidoreductase

Title:

Crystal structure of d-erythronate-4-phosphate dehydrogenase complexed with NAD

Structure:

Erythronate-4-phosphate dehydrogenase. Chain: a, b. Engineered: yes

Source:

Pseudomonas aeruginosa. Organism_taxid: 287. Strain: pao1. Gene: pa1375, pdxb. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.30Å R-factor: 0.229 R-free: 0.259

Authors:

J.Y.Ha,J.H.Lee,K.H.Kim,D.J.Kim,H.H.Lee,H.K.Kim,H.J.Yoon,S.W.Suh

Key ref:

J.Y.Ha et al. (2007). Crystal Structure of d-Erythronate-4-phosphate Dehydrogenase Complexed with NAD. J Mol Biol, 366, 1294-1304. PubMed id: 17217963 DOI: 10.1016/j.jmb.2006.12.038

Date:

04-Dec-06 Release date: 20-Feb-07

Protein chains

Q9I3W9  (PDXB_PSEAE) -  Erythronate-4-phosphate dehydrogenase from Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)

Seq: 380 a.a.

Struc: 380 a.a.

Enzyme reactions

• Enzyme class: E.C.1.1.1.290 - 4-phosphoerythronate dehydrogenase.
• Reaction: 4-phospho-D-erythronate + NAD⁺ = (R)-3-hydroxy-2-oxo-4- phosphooxybutanoate + NADH + H⁺

4-phospho-D-erythronate (Bound ligand (Het Group name = TLA) matches with 64.29% similarity) + NAD(+) (Bound ligand (Het Group name = NAD) corresponds exactly) = (R)-3-hydroxy-2-oxo-4- phosphooxybutanoate + NADH + H(+)

• Cofactor: NAD(+)

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

reference

DOI no: 10.1016/j.jmb.2006.12.038

J Mol Biol 366:1294-1304 (2007)

PubMed id: 17217963

Crystal Structure of d-Erythronate-4-phosphate Dehydrogenase Complexed with NAD.

J.Y.Ha, J.H.Lee, K.H.Kim, d.o. .J.Kim, H.H.Lee, H.K.Kim, H.J.Yoon, S.W.Suh.

ABSTRACT

Pyridoxal-5'-phosphate (the active form of vitamin B6) is an essential cofactor in many enzymatic reactions. While animals lack any of the pathways for de novo synthesis and salvage of vitamin B6, it is synthesized by two distinct biosynthetic routes in bacteria, fungi, parasites, and plants. One of them is the PdxA/PdxJ pathway found in the gamma subdivision of proteobacteria. It depends on the pdxB gene, which encodes erythronate-4-phosphate dehydrogenase (PdxB), a member of the d-isomer specific 2-hydroxyacid dehydrogenase superfamily. Although three-dimensional structures of other functionally related dehydrogenases are available, no structure of PdxB has been reported. To provide the missing structural information and to gain insights into the catalytic mechanism, we have determined the first crystal structure of erythronate-4-phosphate dehydrogenase from Pseudomonas aeruginosa in the ligand-bound state. It is a homodimeric enzyme consisting of 380-residue subunits. Each subunit consists of three structural domains: the lid domain, the nucleotide-binding domain, and the C-terminal dimerization domain. The latter domain has a unique fold and is largely responsible for dimerization. Interestingly, two subunits of the dimeric enzyme are bound with different combinations of ligands in the crystal and they display significantly different conformations. Subunit A is bound with NAD and a phosphate ion, while subunit B, with a more open active site cleft, is bound with NAD and l(+)-tartrate. Our structural data allow a detailed understanding of cofactor and substrate recognition, thus providing substantial insights into PdxB catalysis.

Selected figure(s)

Figure 4.
Figure 4. Conformational difference between subunits A and B of P. aeruginosa PdxB. Stereo surface view of (a) subunit A and (b) subunit B. Stereo view of (c) subunit A, Ile67 and Arg208 are shown in spheres and NAD is shown in sticks, and (d) subunit B, Ile67 and Arg208 are shown in spheres and NAD is shown in sticks. (e) Displacement of Ile67 and Arg208 upon binding l(+)-tartrate. Pink and violet indicate subunits A and B, respectively. Figure 4. Conformational difference between subunits A and B of P. aeruginosa PdxB. Stereo surface view of (a) subunit A and (b) subunit B. Stereo view of (c) subunit A, Ile67 and Arg208 are shown in spheres and NAD is shown in sticks, and (d) subunit B, Ile67 and Arg208 are shown in spheres and NAD is shown in sticks. (e) Displacement of Ile67 and Arg208 upon binding l(+)-tartrate. Pink and violet indicate subunits A and B, respectively.

Figure 5.
Figure 5. A proposed model for the substrate binding to P. aeruginosa PdxB. (a) Chemical structures of l(+)-tartrate and d-erythronate-4-phosphate. (b) Modeled binding of d-erythronate-4-phosphate to P. aeruginosa PdxB. Arg208, Glu237, and His254 in this Figure constitute the catalytic triad in P. aeruginosa PdxB. Figure 5. A proposed model for the substrate binding to P. aeruginosa PdxB. (a) Chemical structures of l(+)-tartrate and d-erythronate-4-phosphate. (b) Modeled binding of d-erythronate-4-phosphate to P. aeruginosa PdxB. Arg208, Glu237, and His254 in this Figure constitute the catalytic triad in P. aeruginosa PdxB.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 366, 1294-1304) copyright 2007.

Figures were selected by an automated process.