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Open Access Research article

New mini- zincin structures provide a minimal scaffold for members of this metallopeptidase superfamily

Christine B Trame12, Yuanyuan Chang3, Herbert L Axelrod2, Ruth Y Eberhardt45, Penelope Coggill45, Marco Punta45 and Neil D Rawlings45*

Author Affiliations

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

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BMC Bioinformatics 2014, 15:1  doi:10.1186/1471-2105-15-1

Published: 3 January 2014

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.

Keywords:
Acel_2062; Metallopeptidase; Zincin; JCSG; Structural genomics