SUBSTRATE AND PSEUDOSUBSTRATE INTERACTIONS WITH PROTEIN-KINASES - DETERMINANTS OF SPECIFICITY

Protein crystallography has revealed that protein kinases have extende d protein-substrate-binding grooves associated with their active sites . Some protein kinases are autoinhibited by a mechanism in which part of their structure, termed a pseudosubstrate, occupies the active site . Substrates and pseudosubstrates occupy overlapping regions within th e extended substrate-binding groove, making multiple specific electros tatic and nonpolar contacts. With masterly economy, Nature has exploit ed the active site in many protein kinases to both recognize substrate s with great specificity and autoregulate by remaining inactive until the appropriate activation signal is received.