PDBsum entry 1sql

Lyase

PDB id: 1sql

Contents

Protein chains

(+ 10 more) 120 a.a. *

Ligands

GUN ×16

Waters ×929

* Residue conservation analysis

PDB id:

1sql

Name:

Lyase

Title:

Crystal structure of 7,8-dihydroneopterin aldolase in complex with guanine

Structure:

Dihydroneopterin aldolase. Chain: a, b, c, d, e, f, g, h, i, j, k, l, m, n, o, p

Source:

Arabidopsis thaliana. Thale cress. Organism_taxid: 3702. Strain: m15[prep4]

Biol. unit:

Octamer (from PQS)

Resolution:

2.20Å R-factor: 0.204 R-free: 0.260

Authors:

S.Bauer,A.K.Schott,V.Illarionova,A.Bacher,R.Huber,M.Fischer

Key ref:

S.Bauer et al. (2004). Biosynthesis of tetrahydrofolate in plants: crystal structure of 7,8-dihydroneopterin aldolase from Arabidopsis thaliana reveals a novel adolase class. J Mol Biol, 339, 967-979. PubMed id: 15165863 DOI: 10.1016/j.jmb.2004.04.034

Date:

19-Mar-04 Release date: 08-Jun-04

Protein chains

Q9SF23  (FOLB1_ARATH) -  Dihydroneopterin aldolase 1 from Arabidopsis thaliana

Seq: 146 a.a.

Struc: 120 a.a.

Enzyme reactions

• Enzyme class: E.C.4.1.2.25 - dihydroneopterin aldolase.
• Pathway: Folate Biosynthesis (late stages)
• Reaction: 7,8-dihydroneopterin = 6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde

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

Key reference

DOI no: 10.1016/j.jmb.2004.04.034

J Mol Biol 339:967-979 (2004)

PubMed id: 15165863

Biosynthesis of tetrahydrofolate in plants: crystal structure of 7,8-dihydroneopterin aldolase from Arabidopsis thaliana reveals a novel adolase class.

S.Bauer, A.K.Schott, V.Illarionova, A.Bacher, R.Huber, M.Fischer.

ABSTRACT

Dihydroneopterin aldolase (DHNA) catalyses a retroaldol reaction yielding 6-hydroxymethyl-7,8-dihydropterin, a biosynthetic precursor of the vitamin, tetrahydrofolate. The enzyme is a potential target for antimicrobial and anti-parasite chemotherapy. A gene specifying a dihydroneopterin aldolase from Arabidopsis thaliana was expressed in a recombinant Escherichia coli strain. The recombinant protein was purified to apparent homogeneity and crystallised using polyethylenglycol as the precipitating agent. The crystal structure was solved by X-ray diffraction analysis at 2.2A resolution. The enzyme forms a D(4)-symmetric homooctamer. Each polypeptide chain is folded into a single domain comprising an antiparallel four-stranded beta-sheet and two long alpha-helices. Four monomers are arranged in a tetrameric ring, and two of these rings form a hollow cylinder. Well defined purine derivatives are found at all eight topologically equivalent active sites. The subunit fold of the enzyme is related to substructures of dihydroneopterin triphosphate epimerase, GTP cyclohydrolase I, and pyruvoyltetrahydropterin synthase, which are all involved in the biosynthesis of pteridine type cofactors, and to urate oxidase, although some members of that superfamily have no detectable sequence similarity. Due to structural and mechanistical differences of DHNA in comparison with class I and class II aldolases, a new aldolase class is proposed.

Selected figure(s)

Figure 9.
Figure 9. Stereo drawing of the A. thaliana DHNA active site with electron density for the bound guanine and the water molecule. Residues that form hydrophobic or hydrogen bond interactions are shown. Ser52 and Tyr53 belong to the adjacent subunit. The final 2F[o] -F[c] electron density map covering the ligand and the water molecule is contoured at 1 sigma.

Figure 12.
Figure 12. Proposed catalytic mechanism of A. thaliana DHNA.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 339, 967-979) copyright 2004.

Figures were selected by an automated process.