Open AccessCrystal Structures of Archaemetzincin Reveal a Moldable Substrate-Binding Site
Author(s) -
Christine Graef,
M. Schacherl,
S. Waltersperger,
Ulrich Baumann
Publication year - 2012
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0043863
Subject(s) - active site , binding site , sequence alignment , cysteine , archaea , structural genomics , conserved sequence , uniprot , chemistry , biology , consensus sequence , computational biology , biochemistry , protein structure , peptide sequence , crystallography , stereochemistry , enzyme , gene
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 Af AmzA (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 Af AmzA 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.