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.

journal_name

BMC Bioinformatics

journal_title

BMC bioinformatics

authors

Trame CB,Chang Y,Axelrod HL,Eberhardt RY,Coggill P,Punta M,Rawlings ND

doi

10.1186/1471-2105-15-1

subject

Has Abstract

pub_date

2014-01-03 00:00:00

pages

1

issn

1471-2105

pii

1471-2105-15-1

journal_volume

15

pub_type

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