Disease relevance of AAH1

• Deaza analogues of adenosine and EHNA were tested as inhibitors of the enzyme adenosine deaminase (ADA) obtained from several sources including human erythrocytes, calf intestine, Saccaromices cerevisiae, Escherichia coli and Takadiastase [1].
• Crystal structure of Staphylococcus aureus tRNA adenosine deaminase TadA in complex with RNA [2].

High impact information on AAH1

• An adenosine deaminase that generates inosine at the wobble position of tRNAs [3].
• The bacterial tRNA adenosine deaminase (TadA) generates inosine by deaminating the adenosine residue at the wobble position of tRNA(Arg-2) [4].
• We have isolated three deletion mutants, srb10, srb11 and saf1 (ybr280c) affecting AAH1 expression during post-diauxic growth and in early stationary phase [5].
• The adenine deaminase encoding gene AAH1 is among the most precociously and tightly downregulated gene upon entry into quiescence [5].
• We show that AAH1 downregulation is not specifically due to glucose exhaustion but is a more general response to nutrient limitation [5].

Biological context of AAH1

• Adenosine deaminase from Saccharomyces cerevisiae: kinetics and interaction with transition and ground state inhibitors [6].

Anatomical context of AAH1

• Among the ribofuranosyl derivatives, 1-deazaadenosine is the best inhibitor, its Ki ranging between 3.5 x 10(-7) and 4 x 10(-5) M for ADA from erythrocytes and Takadiastase respectively [1].

Associations of AAH1 with chemical compounds

• The second enzyme converts adenosine to inosine and in all likelihood is adenosine aminohydrolase (EC 3.5.4.4) [7].
• Inhibition of adenosine deaminase from several sources by deaza derivatives of adenosine and EHNA [1].
• Only ADA from erythrocytes and calf intestine bind EHNA and some of deazaEHNA analogues; 3-deazaEHNA behaves very similarly to EHNA both in affinity and slow binding mechanism, whereas 1-deazaEHNA, though less potent, is a good inhibitor [1].
• The specificity of the yeast enzyme is more restricted than that of mammalian adenosine deaminase, particularly towards the ribose moiety and around position 6 and 1 of the substrate [6].
• Several adenosine analogs, such as coformycin, 2'-deoxycoformycin and erythro-9-(3-nonyl-p-aminobenzyl)adenine (EHNA), which are strong inhibitors of mammalian adenosine deaminase, are much weaker inhibitors of the Saccharomyces cerevisiae enzyme [6].
• Because this mutated residue is an exposed lysine in the Aah1p three-dimensional model, we propose that it is likely to be a major ubiquitylation site [8].

Analytical, diagnostic and therapeutic context of AAH1

• Adenosine deaminase from Saccharomyces Cerevisiae was purified about 1600 fold by salt fractionation, ion exchange and affinity chromatography [9].

References