Functional evolution of PLP-dependent enzymes based on active-site structural similarities

Citations Over Time

Abstract

Families of distantly related proteins typically have very low sequence identity, which hinders evolutionary analysis and functional annotation. Slowly evolving features of proteins, such as an active site, are therefore valuable for annotating putative and distantly related proteins. To date, a complete evolutionary analysis of the functional relationship of an entire enzyme family based on active-site structural similarities has not yet been undertaken. Pyridoxal-5'-phosphate (PLP) dependent enzymes are primordial enzymes that diversified in the last universal ancestor. Using the comparison of protein active site structures (CPASS) software and database, we show that the active site structures of PLP-dependent enzymes can be used to infer evolutionary relationships based on functional similarity. The enzymes successfully clustered together based on substrate specificity, function, and three-dimensional-fold. This study demonstrates the value of using active site structures for functional evolutionary analysis and the effectiveness of CPASS.

Related Papers

• → Structure and chemistry of enzymatic active sites that play a role in the switch and conformation mechanism(2022)45 cited
• → The early evolution of the mega-diverse genus Begonia (Begoniaceae) inferred from organelle DNA phylogenies(2010)35 cited
• → A genetic analysis of some components of reproductive isolation between two closely related species,(1997)31 cited
• → The evolution of embryonic patterning mechanisms in animals(2000)28 cited
• → Detection of Pathways Affected by Positive Selection in Primate Lineages Ancestral to Humans(2017)1 cited