Structural highlights
1lij is a 1 chain structure with sequence from Toxgo. This structure supersedes the now removed PDB entry 1dh1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , |
| Related: | 1lii, 1lik, 1lio |
| Activity: | Adenosine kinase, with EC number 2.7.1.20 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[ADK_TOXGO] ATP-dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives. It is a key purine metabolic enzyme in the opportunistic parasitic protozoan toxoplasma gondii as it cannot synthesize purines de novo.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Adenosine kinase (AK) is a key purine metabolic enzyme from the opportunistic parasitic protozoan Toxoplasma gondii and belongs to the family of carbohydrate kinases that includes ribokinase. To understand the catalytic mechanism of AK, we determined the structures of the T. gondii apo AK, AK:adenosine complex and the AK:adenosine:AMP-PCP complex to 2.55 A, 2.50 A and 1.71 A resolution, respectively. These structures reveal a novel catalytic mechanism that involves an adenosine-induced domain rotation of 30 degrees and a newly described anion hole (DTXGAGD), requiring a helix-to-coil conformational change that is induced by ATP binding. Nucleotide binding also evokes a coil-to-helix transition that completes the formation of the ATP binding pocket. A conserved dipeptide, Gly68-Gly69, which is located at the bottom of the adenosine-binding site, functions as the switch for domain rotation. The synergistic structural changes that occur upon substrate binding sequester the adenosine and the ATP gamma phosphate from solvent and optimally position the substrates for catalysis. Finally, the 1.84 A resolution structure of an AK:7-iodotubercidin:AMP-PCP complex reveals the basis for the higher affinity binding of this prodrug over adenosine and thus provides a scaffold for the design of new inhibitors and subversive substrates that target the T. gondii AK.
Crystal structures of Toxoplasma gondii adenosine kinase reveal a novel catalytic mechanism and prodrug binding.,Schumacher MA, Scott DM, Mathews II, Ealick SE, Roos DS, Ullman B, Brennan RG J Mol Biol. 2000 May 19;298(5):875-93. PMID:10801355[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schumacher MA, Scott DM, Mathews II, Ealick SE, Roos DS, Ullman B, Brennan RG. Crystal structures of Toxoplasma gondii adenosine kinase reveal a novel catalytic mechanism and prodrug binding. J Mol Biol. 2000 May 19;298(5):875-93. PMID:10801355 doi:10.1006/jmbi.2000.3753
