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PDBsum entry 1hka

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protein links
Transferase PDB id
1hka
Jmol
Contents
Protein chain
158 a.a. *
Waters ×236
* Residue conservation analysis
PDB id:
1hka
Name: Transferase
Title: 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase
Structure: 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase. Chain: a. Synonym: hppk. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: folk. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.50Å     R-factor:   0.182    
Authors: B.Xiao,G.Shi,X.Chen,H.Yan,X.Ji
Key ref:
B.Xiao et al. (1999). Crystal structure of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase, a potential target for the development of novel antimicrobial agents. Structure, 7, 489-496. PubMed id: 10378268 DOI: 10.1016/S0969-2126(99)80065-3
Date:
29-Sep-98     Release date:   08-Jun-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

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

 Enzyme reactions 
   Enzyme class: E.C.2.7.6.3  - 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
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
ATP
+ 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine
= AMP
+ (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  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(99)80065-3 Structure 7:489-496 (1999)
PubMed id: 10378268  
 
 
Crystal structure of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase, a potential target for the development of novel antimicrobial agents.
B.Xiao, G.Shi, X.Chen, H.Yan, X.Ji.
 
  ABSTRACT  
 
BACKGROUND: Folate cofactors are essential for life. Mammals derive folates from their diet, whereas most microorganisms must synthesize folates de novo. Enzymes of the folate pathway therefore provide ideal targets for the development of antimicrobial agents. 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), the first reaction in the folate biosynthetic pathway. RESULTS: The crystal structure of HPPK from Escherichia coli has been determined at 1.5 A resolution with a crystallographic R factor of 0.182. The HPPK molecule has a novel three-layered alpha beta alpha fold that creates a valley approximately 26 A long, 10 A wide and 10 A deep. The active center of HPPK is located in the valley and the substrate-binding sites have been identified with the aid of NMR spectroscopy. The HP-binding site is located at one end of the valley, near Asn55, and is sandwiched between two aromatic sidechains. The ATP-binding site is located at the other end of the valley. The adenine base of ATP is positioned near Leu111 and the ribose and the triphosphate extend across and reach the vicinity of HP. CONCLUSIONS: The HPPK structure provides a framework to elucidate structure/function relationships of the enzyme and to analyze mechanisms of pyrophosphoryl transfer. Furthermore, this work may prove useful in the structure-based design of new antimicrobial agents.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. The folate biosynthetic pathway. The abbreviations for the enzymes of the pathway are given: HPPK, 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase; DHPS, dihydropteroate synthase; DHFS, dihydrofolate synthase; and DHFR, dihydrofolate reductase.
 
  The above figure is reprinted by permission from Cell Press: Structure (1999, 7, 489-496) copyright 1999.  
  Figure was 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
19180449 K.S.Keating, S.C.Flores, M.B.Gerstein, and L.A.Kuhn (2009).
StoneHinge: hinge prediction by network analysis of individual protein structures.
  Protein Sci, 18, 359-371.  
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
16997145 A.Nzila (2006).
Inhibitors of de novo folate enzymes in Plasmodium falciparum.
  Drug Discov Today, 11, 939-944.  
15739204 J.Ko, L.F.Murga, P.André, H.Yang, M.J.Ondrechen, R.J.Williams, A.Agunwamba, and D.E.Budil (2005).
Statistical criteria for the identification of protein active sites using Theoretical Microscopic Titration Curves.
  Proteins, 59, 183-195.  
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.  
12211000 O.Keskin, X.Ji, J.Blaszcyk, and D.G.Covell (2002).
Molecular motions and conformational changes of HPPK.
  Proteins, 49, 191-205.  
  11546767 B.Xiao, G.Shi, J.Gao, J.Blaszczyk, Q.Liu, X.Ji, and H.Yan (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.
PDB codes: 1eq0 1eqm
11435118 L.J.Baker, J.A.Dorocke, R.A.Harris, and D.E.Timm (2001).
The crystal structure of yeast thiamin pyrophosphokinase.
  Structure, 9, 539-546.
PDB code: 1ig0
11406387 S.A.Teichmann, A.G.Murzin, and C.Chothia (2001).
Determination of protein function, evolution and interactions by structural genomics.
  Curr Opin Struct Biol, 11, 354-363.  
11080626 J.Blaszczyk, G.Shi, H.Yan, and X.Ji (2000).
Catalytic center assembly of HPPK as revealed by the crystal structure of a ternary complex at 1.25 A resolution.
  Structure, 8, 1049-1058.
PDB codes: 1eqo 1q0n
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.