PDBsum entry 3loo

Transferase

PDB id: 3loo

Contents

Protein chains

335 a.a. *

Ligands

B4P ×3

Metals

_CL ×3

_MG ×3

Waters ×242

* Residue conservation analysis

PDB id:

3loo

Name:

Transferase

Title:

Crystal structure of anopheles gambiae adenosine kinase in complex with p1,p4-di(adenosine-5) tetraphosphate

Structure:

Anopheles gambiae adenosine kinase. Chain: a, b, c. Engineered: yes

Source:

Anopheles gambiae. Organism_taxid: 7165. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.00Å R-factor: 0.201 R-free: 0.248

Authors:

M.-C.Ho,M.B.Cassera,S.C.Almo,V.L.Schramm

Key ref:

M.B.Cassera et al. (2011). A high-affinity adenosine kinase from Anopheles gambiae. Biochemistry, 50, 1885-1893. PubMed id: 21247194

Date:

04-Feb-10 Release date: 02-Feb-11

Protein chains

No UniProt id for this chain

Struc: 335 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.1.20 - adenosine kinase.
• Reaction: adenosine + ATP = AMP + ADP + H⁺

adenosine + ATP (Bound ligand (Het Group name = B4P) matches with 58.49% similarity) = AMP + ADP + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Biochemistry 50:1885-1893 (2011)

PubMed id: 21247194

A high-affinity adenosine kinase from Anopheles gambiae.

M.B.Cassera, M.C.Ho, E.F.Merino, E.S.Burgos, A.Rinaldo-Matthis, S.C.Almo, V.L.Schramm.

ABSTRACT

Genome analysis revealed a mosquito orthologue of adenosine kinase in Anopheles gambiae (AgAK; the most important vector for the transmission of Plasmodium falciparum in Africa). P. falciparum are purine auxotrophs and do not express an adenosine kinase but rely on their hosts for purines. AgAK was kinetically characterized and found to have the highest affinity for adenosine (K(m) = 8.1 nM) of any known adenosine kinase. AgAK is specific for adenosine at the nucleoside site, but several nucleotide triphosphate phosphoryl donors are tolerated. The AgAK crystal structure with a bound bisubstrate analogue Ap(4)A (2.0 Å resolution) reveals interactions for adenosine and ATP and the geometry for phosphoryl transfer. The polyphosphate charge is partly neutralized by a bound Mg(2+) ion and an ion pair to a catalytic site Arg. The AgAK structure consists of a large catalytic core in a three-layer α/β/α sandwich, and a small cap domain in contact with adenosine. The specificity and tight binding for adenosine arise from hydrogen bond interactions of Asn14, Leu16, Leu40, Leu133, Leu168, Phe168, and Thr171 and the backbone of Ile39 and Phe168 with the adenine ring as well as through hydrogen bond interactions between Asp18, Gly64, and Asn68 and the ribosyl 2'- and 3'-hydroxyl groups. The structure is more similar to that of human adenosine kinase (48% identical) than to that of AK from Toxoplasma gondii (31% identical). With this extraordinary affinity for AgAK, adenosine is efficiently captured and converted to AMP at near the diffusion limit, suggesting an important role for this enzyme in the maintenance of the adenine nucleotide pool. mRNA analysis verifies that AgAK transcripts are produced in the adult insects.