Quinoproteins and Cofactors: Expecting the Unexpected

Abstract

Naturally occurring modifications of the standard 20 amino acids expand the repertoire of functional groups available for catalysis within enzyme active sites. A novel class of enzymatic quino-cofactors has been identified over the past decade. These are derived from protein and peptide-bound side chains and include the eukaryotic topa quinone (TPQ) and lysine tyrosyl quinone (LTQ) cofactors, together with the prokaryotic tryptophan tryptophyl quinone (TTQ), cysteine tryptophyl quinone (CTQ) and pyrroloquinoline quinine (PQQ). As an exception to the protein-bound quino-cofactors (TPQ, LTQ, TTQ and CTQ), the precursor to PQQ is generated within a polypeptide chain, followed by its release via proteolysis to yield a freely dissociable cofactor. This presentation will trace the history of the field, followed by a comparison of the properties for TPQ biogenesis (and catalysis) to PQQ biogenesis - with the former occurring via a self-processing mechanism while the latter requires multiple gene products. Many unexpected features have emerged from these studies that include the occurrence of multiple catalytic functions within single enzyme active sites, a non-redox role for a redox active metal center, and the control of molecular oxygen reactivity via non-metal, protein-derived binding pockets. (Supported by NIH GM25765 and GM39296)