For this reason, metallopeptidases such as MMP1 are known as Met-zincins. In MMP1 there is also an important region known as the Met-turn, in which there is a conserved methionine that structurally supports the active site. In a metallopeptidase such as matrix metallopeptidase 1 (MMP1), the zinc ligands are the three histidines within an HEXXHXXGXXH motif. In a metallopeptidase such as thermolysin, the third zinc ligand is usually a glutamic acid, and these peptidases are known as Glu-zincins. Metallopeptidases with an HEXXH motif are known as zincins. In many of these families, but not all, the residues that ligate the zinc ion (referred to here as “ligands”) are two histidines within an HEXXH motif, and a third coordinating residue that is C-terminal to this motif, which can be a glutamic acid, a histidine or an aspartic acid. The zinc ion is tetrahedrally co-ordinated by three residues from the peptidase and a water molecule that becomes activated to be the nucleophile in the catalytic reaction. There are many families of metallopeptidases that bind a single zinc ion required for catalysis. Rather than being an ancestral state, phylogenetic analysis suggests that the mini-zincins are derived from larger proteins.Ī metallopeptidase is a proteolytic enzyme that has one or two metal ions as an integral part of its catalytic machinery located within the active site. 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). It contains the minimum structural features of a member of this protein superfamily, and can be described as a “mini- zincin”. The Acel_2062 protein is structurally related to the zincins. 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. In our crystallographic model there are two molecules in the asymmetric unit and from size-exclusion chromatography, the protein dimerizes in solution. 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. The crystal structure confirmed that the Acel_2062 protein consisted of a single, zincin-like metallopeptidase-like domain. 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. 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 ( HEXX HXXGXX D). The Acel_2062 protein from Acidothermus cellulolyticus is a protein of unknown function.
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