PDBsum entry 2cg8

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protein Protein-protein interface(s) links
Lyase/transferase PDB id
Protein chains
241 a.a. *
248 a.a. *
* Residue conservation analysis
PDB id:
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)
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
28-Feb-06     Release date:   21-Jun-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P59657  (SULD_STRR6) -  Bifunctional folate synthesis protein
270 a.a.
241 a.a.
Protein chain
Pfam   ArchSchema ?
P59657  (SULD_STRR6) -  Bifunctional folate synthesis protein
270 a.a.
248 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: Chains A, B, C, D: E.C.  - 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Folate Biosynthesis (late stages)
      Reaction: ATP + 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine = AMP + (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate
+ 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine
+ (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate
   Enzyme class 2: Chains A, B, C, D: E.C.  - Dihydroneopterin aldolase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Reaction: 2-amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8- dihydropteridine = 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine + glycolaldehyde
2-amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8- dihydropteridine
= 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine
+ 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
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   6 terms 
  Biochemical function     catalytic activity     8 terms  


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.
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.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
17331536 J.Blaszczyk, Y.Li, J.Gan, H.Yan, and X.Ji (2007).
Structural basis for the aldolase and epimerase activities of Staphylococcus aureus dihydroneopterin aldolase.
  J Mol Biol, 368, 161-169.
PDB codes: 2nm2 2nm3
18007032 J.Blaszczyk, Y.Li, S.Cherry, J.Alexandratos, Y.Wu, G.Shaw, J.E.Tropea, D.S.Waugh, H.Yan, and X.Ji (2007).
Structure and activity of Yersinia pestis 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase as a novel target for the development of antiplague therapeutics.
  Acta Crystallogr D Biol Crystallogr, 63, 1169-1177.
PDB code: 2qx0
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