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PDBsum entry 2dhn

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Product complex PDB id
2dhn
Jmol
Contents
Protein chain
121 a.a. *
Ligands
PH2
Waters ×74
* Residue conservation analysis
PDB id:
2dhn
Name: Product complex
Title: Complex of 7,8-dihydroneopterin aldolase from staphylococcus with 6-hydroxymethyl-7,8-dihydropterin at 2.2 a resolution
Structure: 7,8-dihydroneopterin aldolase. Chain: a. Synonym: dhna. Engineered: yes
Source: Staphylococcus aureus. Organism_taxid: 1280. Atcc: atcc 25923. Collection: atcc 25923. Gene: dhna. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Octamer (from PQS)
Resolution:
2.20Å     R-factor:   0.202     R-free:   0.298
Authors: M.Hennig,A.D'Arcy,I.C.Hampele,M.G.P.Page,C.H.Oefner,G.Dale
Key ref: M.Hennig et al. (1998). Crystal structure and reaction mechanism of 7,8-dihydroneopterin aldolase from Staphylococcus aureus. Nat Struct Biol, 5, 357-362. PubMed id: 9586996
Date:
31-Mar-98     Release date:   20-Apr-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P56740  (FOLB_STAAU) -  Dihydroneopterin aldolase
Seq:
Struc:
121 a.a.
121 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.4.1.2.25  - Dihydroneopterin aldolase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Folate Biosynthesis (late stages)
      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
Bound ligand (Het Group name = PH2)
corresponds exactly
+ glycolaldehyde
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     folic acid-containing compound metabolic process   3 terms 
  Biochemical function     lyase activity     2 terms  

 

 
    Added reference    
 
 
Nat Struct Biol 5:357-362 (1998)
PubMed id: 9586996  
 
 
Crystal structure and reaction mechanism of 7,8-dihydroneopterin aldolase from Staphylococcus aureus.
M.Hennig, A.D'Arcy, I.C.Hampele, M.G.Page, C.Oefner, G.E.Dale.
 
  ABSTRACT  
 
Dihydroneopterin aldolase catalyzes the conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin during the de novo synthesis of folic acid from guanosine triphosphate. The gene encoding the dihydroneopterin aldolase from S. aureus has been cloned, sequenced and expressed in Escherichia coli. The protein has been purified for biochemical characterization and its X-ray structure determined at 1.65 A resolution. The protein forms an octamer of 110,000 Mr molecular weight. Four molecules assemble into a ring, and two rings come together to give a cylinder with a hole of at least 13 A diameter. The structure of the binary complex with the product 6-hydroxymethyl-7,8-dihydropterin has defined the location of the active site. The structural information and results of site directed mutagenesis allow an enzyme reaction mechanism to be proposed.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  18931427 J.E.Spoonamore, S.A.Roberts, A.Heroux, and V.Bandarian (2008).
Structure of a 6-pyruvoyltetrahydropterin synthase homolog from Streptomyces coelicolor.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 875-879.
PDB code: 3d7j
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
17388809 Y.Wang, Y.Li, Y.Wu, and H.Yan (2007).
Mechanism of dihydroneopterin aldolase. NMR, equilibrium and transient kinetic studies of the Staphylococcus aureus and Escherichia coli enzymes.
  FEBS J, 274, 2240-2252.  
16997145 A.Nzila (2006).
Inhibitors of de novo folate enzymes in Plasmodium falciparum.
  Drug Discov Today, 11, 939-944.  
16440096 G.Scherperel, H.Yan, Y.Wang, and G.E.Reid (2006).
'Top-down' characterization of site-directed mutagenesis products of Staphylococcus aureus dihydroneopterin aldolase by multistage tandem mass spectrometry in a linear quadrupole ion trap.
  Analyst, 131, 291-302.  
17032756 R.Horst, G.Wider, J.Fiaux, E.B.Bertelsen, A.L.Horwich, and K.Wüthrich (2006).
Proton-proton Overhauser NMR spectroscopy with polypeptide chains in large structures.
  Proc Natl Acad Sci U S A, 103, 15445-15450.  
17176045 Y.Wang, Y.Li, and H.Yan (2006).
Mechanism of dihydroneopterin aldolase: functional roles of the conserved active site glutamate and lysine residues.
  Biochemistry, 45, 15232-15239.  
15767583 S.G.Van Lanen, J.S.Reader, M.A.Swairjo, V.de Crécy-Lagard, B.Lee, and D.Iwata-Reuyl (2005).
From cyclohydrolase to oxidoreductase: discovery of nitrile reductase activity in a common fold.
  Proc Natl Acad Sci U S A, 102, 4264-4269.  
15997470 W.Huber (2005).
A new strategy for improved secondary screening and lead optimization using high-resolution SPR characterization of compound-target interactions.
  J Mol Recognit, 18, 273-281.  
12111724 A.Bermingham, and J.P.Derrick (2002).
The folic acid biosynthesis pathway in bacteria: evaluation of potential for antibacterial drug discovery.
  Bioessays, 24, 637-648.  
12039964 V.Illarionova, W.Eisenreich, M.Fischer, C.Haussmann, W.Romisch, G.Richter, and A.Bacher (2002).
Biosynthesis of tetrahydrofolate. Stereochemistry of dihydroneopterin aldolase.
  J Biol Chem, 277, 28841-28847.  
10737935 N.Colloc'h, A.Poupon, and J.P.Mornon (2000).
Sequence and structural features of the T-fold, an original tunnelling building unit.
  Proteins, 39, 142-154.  
11050425 R.Riek, K.Pervushin, and K.Wüthrich (2000).
TROSY and CRINEPT: NMR with large molecular and supramolecular structures in solution.
  Trends Biochem Sci, 25, 462-468.  
11188700 S.W.Muchmore, J.Olson, R.Jones, J.Pan, M.Blum, J.Greer, S.M.Merrick, P.Magdalinos, and V.L.Nienaber (2000).
Automated crystal mounting and data collection for protein crystallography.
  Structure, 8, R243-R246.  
10449740 K.V.Pervushin, G.Wider, R.Riek, and K.Wüthrich (1999).
The 3D NOESY-[(1)H,(15)N,(1)H]-ZQ-TROSY NMR experiment with diagonal peak suppression.
  Proc Natl Acad Sci U S A, 96, 9607-9612.  
10220394 R.Riek, G.Wider, K.Pervushin, and K.Wüthrich (1999).
Polarization transfer by cross-correlated relaxation in solution NMR with very large molecules.
  Proc Natl Acad Sci U S A, 96, 4918-4923.  
10378270 T.Ploom, C.Haussmann, P.Hof, S.Steinbacher, A.Bacher, J.Richardson, and R.Huber (1999).
Crystal structure of 7,8-dihydroneopterin triphosphate epimerase.
  Structure, 7, 509-516.
PDB code: 1b9l
9875848 C.S.Raman, H.Li, P.Martásek, V.Král, B.S.Masters, and T.L.Poulos (1998).
Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center.
  Cell, 95, 939-950.
PDB codes: 1nse 2nse 3nse 4nse
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.