2.A.59 The Arsenical Resistance-3 (ACR3) Family

Two proteins of the ACR3 family have been functionally characterized. These proteins are the ACR3 protein of Saccharomyces cerevisiae, also called the ARR3 protein (Wysocki et al., 1997), and the 'ArsB' protein of Bacillus subtilis (Sato and Kobayashi, 1998). The latter protein is not related to ArsB of E. coli. The former yeast protein is present in the plasma membrane and pumps arsenite and antimonite, but not arsenate, tellurite, cadmium or phenylarsine oxide out of the cell in response to the pmf.  It uses a proton antiport mechanism to extrude the anions with low affinity (Maciaszczyk-Dziubinska et al., 2011). The Bacillus protein exports both arsenite and antimonite. The exact transport mechanism is not established. Bacillus Acr3 probably has a 10 TMS topology (Aaltonen and Silow, 2008).

ACR3 of S. cerevisiae is 404 amino acyl residues long and exhibits 10 putative transmembrane α-helical spanners (TMSs). Homologues are found in Mycobacterium tuberculosis (498 aas; gbZ80225), Archaeoglobus fulgidus (370 aas; gbAE001071), Methanobacterium thermoautotrophicum (365 aas; gbAE000865) and Synechocystis (383 aas; spP74311). Thus, members of the ACR3 family are found in bacteria, archaea and eukarya. Sequence similarity of several members of the Acr3 family with members of the bile acid:Na⁺ symporter (BASS) family (TC #2.A.28) is sufficient to establish homology. The ACR3 family belongs to the BART superfamily (Mansour et al., 2007).  When an ACR3 protein functions with an ATPase, that ATPase is a member of the ArsA superfamily.

Bioinformatic analyses have revealed that some ACR3 porters are involved in operons together with ArsA-like ATPases, implying that some of these porters may be driven by ATP hydrolysis as primary active transporters (Castillo and Saier, 2010). This may occur in addition to or instead of the secondary active transport mechanism established for ACR3 members noted above. Homologous ATPases are found in families 3.A.4, 3.A.19 and 3.A.21 as well as 2.A.59. A region of the ABC ATPase (3.A.1.26.8; the ribose transporter) shows significant sequence similarity to the ArsA under 3.A.19.1.1 (28% identical; 49% similarity, 0 gaps, e^-5) as revealed by TC Blast.

The generalized reaction catalyzed by members of the ACR3 family is:

Arsenite or antimonite (in) Arsenite or antimonite (out)