title: New mini- zincin structures provide a minimal scaffold for members of this metallopeptidase superfamily.
abstract: BACKGROUND
  The Acel_2062 protein from Acidothermus cellulolyticus is a protein of unknown function. Initial sequence analysis predicted that it was a metallopeptidase from the presence of a motif conserved amongst the Asp-zincins, which are peptidases that contain a single, catalytic zinc ion ligated by the histidines and aspartic acid within the motif (HEXXHXXGXXD). The Acel_2062 protein was chosen by the Joint Center for Structural Genomics for crystal structure determination to explore novel protein sequence space and structure-based function annotation.
  
  
  RESULTS
  The crystal structure confirmed that the Acel_2062 protein consisted of a single, zincin-like metallopeptidase-like domain. The Met-turn, a structural feature thought to be important for a Met-zincin because it stabilizes the active site, is absent, and its stabilizing role may have been conferred to the C-terminal Tyr113. In our crystallographic model there are two molecules in the asymmetric unit and from size-exclusion chromatography, the protein dimerizes in solution. A water molecule is present in the putative zinc-binding site in one monomer, which is replaced by one of two observed conformations of His95 in the other.
  
  
  CONCLUSIONS
  The Acel_2062 protein is structurally related to the zincins. It contains the minimum structural features of a member of this protein superfamily, and can be described as a "mini- zincin". There is a striking parallel with the structure of a mini-Glu-zincin, which represents the minimum structure of a Glu-zincin (a metallopeptidase in which the third zinc ligand is a glutamic acid). Rather than being an ancestral state, phylogenetic analysis suggests that the mini-zincins are derived from larger proteins.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Trame
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Chang
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Axelrod
authors.forename: Ruth Y
authors.initials: RY
authors.lastname: Eberhardt
authors.forename: Penelope
authors.initials: P
authors.lastname: Coggill
authors.forename: Marco
authors.initials: M
authors.lastname: Punta
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, CB10 1SA, UK. ndr@ebi.ac.uk.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Rawlings
mesh_terms: D000192:Actinomycetales / Q000737:chemistry / Q000201:enzymology; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D045726:Metalloproteases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D021122:Protein Subunits; D016415:Sequence Alignment; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D021122:Protein Subunits; D045726:Metalloproteases; D015032:Zinc