PDBsum entry: 1p9b

Ligase

PDB id: 1p9b

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

Protein chain

Q9U8D3  (PURA_PLAFA) -  Adenylosuccinate synthetase

Seq: 442 a.a.

Struc: 424 a.a.

Enzyme reactions

• Enzyme class: E.C.6.3.4.4 - Adenylosuccinate synthase.
• 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 

• Cellular component: cytoplasm (1 term)
• Biological process: purine nucleotide biosynthetic process (1 term)
• 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.