Improving function assignment for metalloenzymes through active site alignment using ProMOL/PyMOL

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Metal ions are an integral part of many proteins, contributing to both the structure and function of the enzyme. A full representation of Metal Macie catalytic site motif set has been created and tested as 3‐dimensional distance‐based motifs using ProMOL, a plugin for the PyMOL molecular graphics environment that utilizes the 3‐dimensional visualization and measurement capacities of PyMOL to align enzyme active sites with a collection of annotated active sites found in our motif template library. ProMOL uses active site alignment to predict enzyme function for proteins of unknown function. To date our group has focused on active sites consisting solely of the 20 canonical amino acids. With this effort, we have expanded our library of motifs to include metalloenzymes, as nearly 40% of all the PDB structures contain at least one metal ion. The purpose for this initiative can be understood by looking at the number of structures in the Protein Data Bank that are labeled as having “unknown function”; to date, there are 3945 such structures in the Protein Data Bank. More than 50 motif templates of enzyme active sites that contain metal ions have been created and tested with ProMOL. Supported by NIGMS 2R15GM078077‐02, 3R15GM078077‐02S1 and 3R15GM078077‐02S2.