PDBsum entry 2cg8

Lyase/transferase

PDB id: 2cg8

Contents

Protein chains

241 a.a. *

248 a.a. *

* Residue conservation analysis

PDB id:

2cg8

Name:

Lyase/transferase

Title:

The bifunctional dihydroneopterin aldolase 6-hydroxymethyl-7,8- dihydropterin synthase from streptococcus pneumoniae

Structure:

Dihydroneopterin aldolase 6-hydroxymethyl-7,8-dihydropterin synthase. Chain: a, b, c, d. Synonym: dihydroneopterin aldolase, dhna, 2-amino-4-hydroxy-6- hydroxymethyldihydropteridine pyrophosphokinase, 7,8-dihydro-6- hydroxymethylpterin pyrophosphokinase, 6-hydroxymethyl-7,8- dihydropterin pyrophosphokinase, hppk, pppk. Engineered: yes

Source:

Streptococcus pneumoniae. Organism_taxid: 1313. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Octamer (from PDB file)

Resolution:

2.90Å R-factor: 0.216 R-free: 0.241

Authors:

A.Garcon,C.Levy,J.P.Derrick

Key ref:

A.Garçon et al. (2006). Crystal structure of the bifunctional dihydroneopterin aldolase/6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase from Streptococcus pneumoniae. J Mol Biol, 360, 644-653. PubMed id: 16781731 DOI: 10.1016/j.jmb.2006.05.038

Date:

28-Feb-06 Release date: 21-Jun-06

Protein chains

P59657  (SULD_STRR6) -  Bifunctional folate synthesis protein from Streptococcus pneumoniae (strain ATCC BAA-255 / R6)

Seq: 270 a.a.

Struc: 241 a.a.

Protein chain

P59657  (SULD_STRR6) -  Bifunctional folate synthesis protein from Streptococcus pneumoniae (strain ATCC BAA-255 / R6)

Seq: 270 a.a.

Struc: 248 a.a.

Enzyme reactions

• Enzyme class 1: Chains A, B, C, D: E.C.2.7.6.3 - 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase.
• Pathway: Folate Biosynthesis (late stages)
• Reaction: 6-hydroxymethyl-7,8-dihydropterin + ATP = (7,8-dihydropterin-6-yl)methyl diphosphate + AMP + H⁺
• Cofactor: Mg(2+)
• Enzyme class 2: Chains A, B, C, D: E.C.4.1.2.25 - dihydroneopterin aldolase.

Pathway:

• Reaction: 7,8-dihydroneopterin = 6-hydroxymethyl-7,8-dihydropterin + glycolaldehyde

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.2006.05.038

J Mol Biol 360:644-653 (2006)

PubMed id: 16781731

Crystal structure of the bifunctional dihydroneopterin aldolase/6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase from Streptococcus pneumoniae.

A.Garçon, C.Levy, J.P.Derrick.

ABSTRACT

The enzymes dihydroneopterin aldolase (DHNA) and 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyse two consecutive steps in the biosynthesis of folic acid. Neither of these enzymes has a counterpart in mammals, and they have therefore been suggested as ideal targets for antimicrobial drugs. Some of the enzymes within the folate pathway can occur as bi- or trifunctional complexes in bacteria and parasites, but the way in which bifunctional DHNA-HPPK enzymes are assembled is unclear. Here, we report the determination of the structure at 2.9 A resolution of the DHNA-HPPK (SulD) bifunctional enzyme complex from the respiratory pathogen Streptococcus pneumoniae. In the crystal, DHNA is assembled as a core octamer, with 422 point group symmetry, although the enzyme is active as a tetramer in solution. Individual HPPK monomers are arranged at the ends of the DHNA octamer, making relatively few contacts with the DHNA domain, but more extensive interactions with adjacent HPPK domains. As a result, the structure forms an elongated cylinder, with the HPPK domains forming two tetramers at each end. The active sites of both enzymes face outward, and there is no clear channel between them that could be used for channelling substrates. The HPPK-HPPK interface accounts for about one-third of the total area between adjacent monomers in SulD, and has levels of surface complementarity comparable to that of the DHNA-DHNA interfaces. There is no "linker" polypeptide between DHNA and HPPK, reducing the conformational flexibility of the HPPK domain relative to the DHNA domain. The implications for the organisation of bi- and trifunctional enzyme complexes within the folate biosynthesis pathway are discussed.

Selected figure(s)

Figure 1.
Figure 1. Reactions catalysed by DHNA, HPPK and DHPS.

Figure 4.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2006, 360, 644-653) copyright 2006.

Figures were selected by the author.