PDBsum entry 1eqm

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Transferase PDB id
Protein chain
158 a.a. *
Waters ×258
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of binary complex of 6-hydroxymethyl-7,8- dihydropterin pyrophosphokinase with adenosine-5'- diphosphate
Structure: 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase. Chain: a. Synonym: hppk. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
1.50Å     R-factor:   0.190     R-free:   0.263
Authors: B.Xiao,J.Blaszczyk,X.Ji
Key ref:
B.Xiao et al. (2001). Unusual conformational changes in 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase as revealed by X-ray crystallography and NMR. J Biol Chem, 276, 40274-40281. PubMed id: 11546767 DOI: 10.1074/jbc.M103837200
05-Apr-00     Release date:   05-Apr-01    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P26281  (HPPK_ECOLI) -  2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase
159 a.a.
158 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: 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
Bound ligand (Het Group name = ADP)
matches with 87.00% similarity
+ 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine
+ (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     phosphorylation   4 terms 
  Biochemical function     nucleotide binding     6 terms  


DOI no: 10.1074/jbc.M103837200 J Biol Chem 276:40274-40281 (2001)
PubMed id: 11546767  
Unusual conformational changes in 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase as revealed by X-ray crystallography and NMR.
B.Xiao, G.Shi, J.Gao, J.Blaszczyk, Q.Liu, X.Ji, H.Yan.
The crystal structure of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) in complex with MgADP has been determined at 1.5-A resolution with a crystallographic R factor of 0.191. The solution structure of HPPK in complex with Mg(2+) and beta,gamma-methyleneadenosine 5'-triphosphate (MgAMPPCP) has been determined using a simulated annealing protocol with 3,523 experimental NMR restraints. The root mean square deviation of the ensemble of 20 refined conformers that represent the solution structure from the mean coordinate set derived from them is 0.74 +/- 0.26 A for all backbone atoms and 0.49 +/- 0.22 A when residues Pro(14), Pro(44)-Gln(50), and Arg(84)-Pro(91) are excluded. Binding of MgADP causes significant changes in the conformation and dynamical property of three loops of HPPK that are involved in catalysis. A dramatic, unusual conformational change is that loop 3 moves away from the active center significantly with some residues moving by >17 A. The binding of MgADP also stabilizes loop 1 and loop 3 but makes loop 2 more mobile. Very similar conformational and dynamical changes are observed in the NMR solution structure of HPPK.MgAMPPCP. The conformational and dynamical changes may play important roles in both substrate binding and product release in the catalytic cycle.
  Selected figure(s)  
Figure 2.
Fig. 2. Stereo view of MgADP-protein interactions. a and b illustrate the interactions of protein with two distinct conformations of ADP. The models are illustrated as ball-and-sticks with filled bonds for protein and open bonds for ADP. Dashed lines represent electrostatic interactions. Atomic color is used with carbon in black, nitrogen in blue, oxygen in red, magnesium in green, and phosphorus in pink. The figure was made with the program Molscript (22).
Figure 8.
Fig. 8. Induced fit in HPPK from apo-HPPK (green) to HPPK·HP·MgAMPCPP (yellow) (a) and from apo-HPPK (green) to HPPK·MgADP (yellow) (b). In panel a, the side chains of apo-HPPK are shown in green and those of HPPK·HP·MgAMPCPP in gray; the two Mg2+ ions are in cyan. In panel b, the side chains of apo-HPPK are shown in green and those of HPPK·MgADP in gray; the Mg2+ ion of HPPK·MgADP is in cyan (Mg1); and the side chains of Asp95 and the two Mg2+ ions (Mg2 and Mg3) of HPPK·HP·MgAMPCPP are in orange. The figure was made with the program Molscript (22) and Raster3D (23, 24).
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 40274-40281) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21152407 C.W.Pemble, P.K.Mehta, S.Mehra, Z.Li, A.Nourse, R.E.Lee, and S.W.White (2010).
Crystal structure of the 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase•dihydropteroate synthase bifunctional enzyme from Francisella tularensis.
  PLoS One, 5, e14165.
PDB codes: 3mcm 3mcn 3mco
17680687 M.Brylinski, and J.Skolnick (2008).
What is the relationship between the global structures of apo and holo proteins?
  Proteins, 70, 363-377.  
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
17362087 M.R.Yun, N.Mousseau, and P.Derreumaux (2007).
Sampling small-scale and large-scale conformational changes in proteins and molecular complexes.
  J Chem Phys, 126, 105101.  
15821168 R.Yang, M.C.Lee, H.Yan, and Y.Duan (2005).
Loop conformation and dynamics of the Escherichia coli HPPK apo-enzyme and its binary complex with MgATP.
  Biophys J, 89, 95.  
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.  
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 codes are shown on the right.