1a4m
From Proteopedia
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ADA STRUCTURE COMPLEXED WITH PURINE RIBOSIDE AT PH 7.0
Overview
Adenosine deaminase, which catalyzes the irreversible hydrolytic, deamination of adenosine nucleosides to inosine nucleosides and ammonia, is a key enzyme in purine metabolism and lymphoid development. The X-ray, structures of murine adenosine deaminase with bound potent inhibitors (Ki, values approximately 10(-13) M) (8R)-hydroxyl-2'-deoxycoformycin, (pentostatin), a transition state analogue, and, (6S)-hydroxyl-1,6-dihydropurine riboside, a reaction coordinate analogue, have been determined and refined to resolutions of 2.6 and 1.95 A, respectively. Crystals of both complexes were obtained at pH 7, where the, enzyme is fully active, in an identical space group with the asymmetric, unit containing four molecules. In addition to the very high degree of, similarity between the four independent molecules in each complex, structure, there is also considerable structural similarity of the complex, with the dihydropurine riboside with that of an identical complex, previously determined at pH 4.2 where the enzyme is 20% active. The, interactions between the enzyme and the two analogues are extremely, similar. These include the coordination of the 8R- or 6S-hydroxyl group of, the analogues to the Zn2+ which mainly contributes to the strong potency, and very high degree of stereospecificity of inhibition by these, analogues. The interactions are further indicative of the structural and, chemical requirements of substrates. These structures and recent, site-directed mutagenesis have further shed light on the catalytic, mechanism of the enzyme.
About this Structure
1A4M is a Single protein structure of sequence from Mus musculus with ZN and PRH as ligands. Active as Adenosine deaminase, with EC number 3.5.4.4 Structure known Active Site: . Full crystallographic information is available from OCA.
Reference
Complexes of adenosine deaminase with two potent inhibitors: X-ray structures in four independent molecules at pH of maximum activity., Wang Z, Quiocho FA, Biochemistry. 1998 Jun 9;37(23):8314-24. PMID:9622483
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