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PDBsum entry 1p9b

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protein ligands metals links
Ligase PDB id
1p9b
Jmol
Contents
Protein chain
424 a.a. *
Ligands
NO3
IMO
HDA
GDP
Metals
_MG
Waters ×278
* Residue conservation analysis
PDB id:
1p9b
Name: Ligase
Title: Structure of fully ligated adenylosuccinate synthetase from falciparum
Structure: Adenylosuccinate synthetase. Chain: a. Engineered: yes
Source: Plasmodium falciparum. Malaria parasite p. Falciparum. Organism_taxid: 5833. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PDB file)
Resolution:
2.00Å     R-factor:   0.199     R-free:   0.241
Authors: K.Eaazhisai,R.Jayalakshmi,P.Gayathri,R.P.Anand,K.Sumathy,H.B M.R.Murthy
Key ref:
K.Eaazhisai et al. (2004). Crystal structure of fully ligated adenylosuccinate synthetase from Plasmodium falciparum. J Mol Biol, 335, 1251-1264. PubMed id: 14729341 DOI: 10.1016/j.jmb.2003.11.036
Date:
10-May-03     Release date:   03-Feb-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9U8D3  (PURA_PLAFA) -  Adenylosuccinate synthetase
Seq:
Struc:
442 a.a.
424 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.6.3.4.4  - Adenylosuccinate synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
AMP and GMP Biosynthesis
      Reaction: GTP + IMP + L-aspartate = GDP + phosphate + N6-(1,2-dicarboxyethyl)- AMP
GTP
+
IMP
Bound ligand (Het Group name = IMO)
matches with 85.19% similarity
+
L-aspartate
Bound ligand (Het Group name = HDA)
matches with 41.67% similarity
=
GDP
Bound ligand (Het Group name = GDP)
corresponds exactly
+ phosphate
+ N(6)-(1,2-dicarboxyethyl)- AMP
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     'de novo' AMP biosynthetic process   3 terms 
  Biochemical function     nucleotide binding     6 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.jmb.2003.11.036 J Mol Biol 335:1251-1264 (2004)
PubMed id: 14729341  
 
 
Crystal structure of fully ligated adenylosuccinate synthetase from Plasmodium falciparum.
K.Eaazhisai, R.Jayalakshmi, P.Gayathri, R.P.Anand, K.Sumathy, H.Balaram, M.R.Murthy.
 
  ABSTRACT  
 
In the absence of the de novo purine nucleotide biosynthetic pathway in parasitic protozoa, purine salvage is of primary importance for parasite survival. Enzymes of the salvage pathway are, therefore, good targets for anti-parasitic drugs. Adenylosuccinate synthetase (AdSS), catalysing the first committed step in the synthesis of AMP from IMP, is a potential target for anti-protozoal chemotherapy. We report here the crystal structure of adenylosuccinate synthetase from the malaria parasite, Plasmodium falciparum, complexed to 6-phosphoryl IMP, GDP, Mg2+ and the aspartate analogue, hadacidin at 2 A resolution. The overall architecture of P. falciparum AdSS (PfAdSS) is similar to the known structures from Escherichia coli, mouse and plants. Differences in substrate interactions seen in this structure provide a plausible explanation for the kinetic differences between PfAdSS and the enzyme from other species. Additional hydrogen bonding interactions of the protein with GDP may account for the ordered binding of substrates to the enzyme. The dimer interface of PfAdSS is also different, with a pronounced excess of positively charged residues. Differences highlighted here provide a basis for the design of species-specific inhibitors of the enzyme.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Purine salvage pathway in Plasmodium falciparum. Inosine monophosphate (IMP), adenylosuccinate (ADS), adenosine monophosphate (AMP), xanthosine monophosphate (XMP), guanosine monophosphate (GMP).
Figure 2.
Figure 2. Stereo diagram of the active site of the fully ligated PfAdSS. The Figure also shows the electron density corresponding to the ligands from a 2F[obs] -F[calc] omit map contoured at 1.0s, using a cover radius of 1.5 Å. This Figure was prepared with the program BOBSCRIPT.[38.]
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 335, 1251-1264) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20807400 C.Huthmacher, A.Hoppe, S.Bulik, and H.G.Holzhütter (2010).
Antimalarial drug targets in Plasmodium falciparum predicted by stage-specific metabolic network analysis.
  BMC Syst Biol, 4, 120.  
19296440 B.Taneja, J.Yadav, T.K.Chakraborty, and S.K.Brahmachari (2009).
An Indian effort towards affordable drugs: "generic to designer drugs".
  Biotechnol J, 4, 348-360.  
17875391 P.Gayathri, H.Balaram, and M.R.Murthy (2007).
Structural biology of plasmodial proteins.
  Curr Opin Struct Biol, 17, 744-754.  
17193183 I.M.Lagoja, and P.Herdewijn (2005).
A potential prebiotic route to adenine from hypoxanthine.
  Chem Biodivers, 2, 923-927.  
16388128 U.Tatu, S.Jain, and P.P.Priya (2005).
Whither genome research: of man, mosquito and malaria.
  J Biosci, 30, 567-571.  
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.