{PDOC51995}
{PS51995; ATLF}
{BEGIN}
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* Anthrax toxin lethal factor (ATLF)-like domain profile *
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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 beta-sheet and a helical
bundle backing  the beta-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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: March 2022 / First entry.

[ 1] Pannifer A.D., Wong T.Y., Schwarzenbacher R., Renatus M., Petosa C.,
     Bienkowska J., Lacy D.B., Collier R.J., Park S., Leppla S.H.,
     Hanna P., Liddington R.C.
     "Crystal structure of the anthrax lethal factor."
     Nature 414:229-233(2001).
     PubMed=11700563; DOI=10.1038/n35101998
[ 2] Shen Y., Zhukovskaya N.L., Guo Q., Florian J., Tang W.-J.
     "Calcium-independent calmodulin binding and two-metal-ion catalytic
     mechanism of anthrax edema factor."
     EMBO. J. 24:929-941(2005).
     PubMed=15719022; DOI=10.1038/sj.emboj.7600574
[ 3] Visschedyk D., Rochon A., Tempel W., Dimov S., Park H.-W.,
     Merrill A.R.
     "Certhrax toxin, an anthrax-related ADP-ribosyltransferase from
     Bacillus cereus."
     J. Biol. Chem. 287:41089-41102(2012).
     PubMed=22992735; DOI=10.1074/jbc.M112.412809
[ 4] Hensbergen P.J., Klychnikov O.I., Bakker D., van Winden V.J.C., Ras N.,
     Kemp A.C., Cordfunke R.A., Dragan I., Deelder A.M., Kuijper E.J.,
     Corver J., Drijfhout J.W., van Leeuwen H.C.
     "A novel secreted metalloprotease (CD2830) from Clostridium difficile
     cleaves specific proline sequences in LPXTG cell surface proteins."
     Mol. Cell. Proteomics. 13:1231-1244(2014).
     PubMed=24623589; DOI=10.1074/mcp.M113.034728
[ 5] Schacherl M., Pichlo C., Neundorf I., Baumann U.
     "Structural Basis of Proline-Proline Peptide Bond Specificity of the
     Metalloprotease Zmp1 Implicated in Motility of Clostridium
     difficile."
     Structure 23:1632-1642(2015).
     PubMed=26211609; DOI=10.1016/j.str.2015.06.018
[ 6] Klychnikov O.I., Shamorkina T.M., Weeks S.D., van Leeuwen H.C.,
     Corver J., Drijfhout J.W., van Veelen P.A., Sluchanko N.N.,
     Strelkov S.V., Hensbergen P.J.
     "Discovery of a new Pro-Pro endopeptidase, PPEP-2, provides
     mechanistic insights into the differences in substrate specificity
     within the PPEP family."
     J. Biol. Chem. 293:11154-11165(2018).
     PubMed=29794027; DOI=10.1074/jbc.RA118.003244

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