New mini- zincin structures provide a minimal scaffold for members of this metallopeptidase superfamily
1 Joint Center for Structural Genomics, La Jolla, CA, 92037, USA
2 Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA, 94025, USA
3 Sandford-Burnham Institute, La Jolla, CA, 92037, USA
4 Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, CB10 1SA, UK
5 European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridgeshire, CB10 1SD, UK
BMC Bioinformatics 2014, 15:1 doi:10.1186/1471-2105-15-1Published: 3 January 2014
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.
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.
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.