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Factors Governing the Different Functions of Zn2+-Sites with Identical Ligands in Proteins
journal contribution
posted on 2019-09-10, 19:38 authored by Yu-Ming Lee, Cédric Grauffel, Ting Chen, Karen Sargsyan, Carmay LimIn
Zn-proteins, structural Zn-sites are mostly
Cys-rich lined by two or more Cys residues, whereas catalytic Zn-sites usually contain His or Asp/Glu residues and a water molecule.
Here, we reveal many examples outside this trend with Zn2+ bound to ligands commonly found in both structural
and catalytic Zn-sites, namely, Zn-CC(C/H)x (x = D, E, or H2O) sites. We show that these atypical
Zn-sites are found in all known life forms (i.e., eukaryotes, bacteria,
archaea, and viruses) and can serve structural roles in some proteins
but catalytic roles in others. By calculating the physical properties
of these atypical Zn-binding sites, we elucidate why Zn-CC(C/H)x sites of the same composition can serve structural and
catalytic roles in proteins. Furthermore, we found new sequence/structural
motifs characteristic of catalytic Zn-CCHw sites
and provide guidelines to predict the structural/catalytic role of
atypical Zn-CC(C/H)x sites of unknown function. We
discuss how our results could help to design inhibitors targeting
catalytic Zn-CC(C/H) H2O sites.