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Updated: May 19, 2026
Crystallization and Structural Determination of an Enzyme:Substrate Complex by Serial Crystallography in a Versatile Microfluidic Chip
Published on: March 20, 2021
Crystal structures of archaemetzincin reveal a moldable substrate-binding site
Christine Graef1, Magdalena Schacherl, Sandro Waltersperger
1Department of Chemistry and Biochemistry, University of Bern, Bern, Switzerland.
Background:
Archaemetzincins are metalloproteases occurring in archaea and some mammalia. They are distinct from all the other metzincins by their extended active site consensus sequence HEXXHXXGXXHCX(4)CXMX(17)CXXC featuring four conserved cysteine residues. Very little is known about their biological importance and structure-function relationships.
Principal Findings:
Here we present three crystal structures of the archaemetzincin AfAmzA (Uniprot O29917) from Archaeoglobus fulgidus, revealing a metzincin architecture featuring a zinc finger-like structural element involving the conserved cysteines of the consensus motif. The active sites in all three structures are occluded to different extents rendering the enzymes proteolytically inactive against a large variety of tested substrates. Owing to the different ligand binding there are significant differences in active site architecture, revealing a large flexibility of the loops covering the active site cleft.
Conclusions:
The crystal structures of AfAmzA provide the structural basis for the lack of activity in standard proteolytic assays and imply a triggered activity onset upon opening of the active site cleft.
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