Functional Evolution of PLP-dependent Enzymes based on Active-Site Structural Similarities

Authors

• Jonathan Catazaro, University of Nebraska-LincolnFollow
• Adam Caprez, University of Nebraska-LincolnFollow
• Ashu Guru, University of Nebraska-LincolnFollow
• David Swanson, University of Nebraska-LincolnFollow
• Robert Powers, University of Nebraska - LincolnFollow

Document Type

Article

Date of this Version

2014

Citation

Proteins. 2014 October ; 82(10): 2597–2608. doi:10.1002/prot.24624.

Comments

Copyright 2014 Wiley Periodicals, Inc. Used by permission.

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.