The ~200-residue anthrax toxin lethal factor (ATLF)-like domain is found in one or two copies in the following proteins:

• Bacillus anthracis Lethal factor (LF), a highly specific protease that cleaves members of the mitogen-activated protein kinase kinase (MAPKK) family near to their amino termini, leading to the inhibition of one or more signaling pathways. LF comprises four domains: domain I binds the membrane-translocating component of anthrax toxin, the protective antigen (PA); domains II, III and IV together create a long deep groove that holds the 16-residue N-terminal tail of MAPKK-2 before cleavage. Domain II resembles the ADP-ribosylating toxin from Bacillus cereus, but the active site has been mutated and recruited to augment substrate recognition. Domain III is inserted into domain II, and seems to have arisen from a repeated duplication of a structural element of domain II. Domain IV is distantly related to the zinc metalloprotease family, and contains the catalytic centre; it also resembles domain I [1].
• Bacillus anthracis Edema factor (EF), a key anthrax exotoxin. It has an anthrax protective antigen-binding domain (PABD) and a calcium- and calmodulin-dependent adenylyl cyclase domain, which catalyzes the formation of cAMP and also affects cell signaling and ion fluxes [2].
• Bacillus cereus Certhrax Toxin, an Anthrax-related ADP-ribosyltransferase. It has two domains, one that binds protective antigen and another that has ADP-ribosyltransferase activity [3].
• Clostridium difficile Pro-Pro endopeptidase (PPEP-1, previously known as Zmp1), which has a remarkable preference for hydrolyzing a Pro–Pro bond [4,5].
• Paenibacillus alvei PPEP-2, one of the PPEP-1 homologs [6].

The ATLF-like domain acts either as a metalloprotease domain, forming the M34 family of metalloendopeptidases, (ATLF domain IV, PPEP-1 and 2) or as an anthrax protective antigen-binding domain (PABD) (ATLF domain I and EF and Certhrax PABD).

The ATLF-like domain is composed of a four-stranded β-sheet and a helical bundle backing the β-sheet (see <PDB:A0P>). All catalytically active ATLF-like domains exhibit the conserved sequence motif HEXXH, where the two histidines ligate the catalytic zinc ion, and the glutamic acid acts as catalytic base activating a zinc-bound water molecule for nucleophilic attack on the scissile peptide bond [1,2,3,5,6].

The profile we developed covers the entire ATLF-like domain.