Substrate and pseudosubstrate interactions with protein kinases: determinants of specificity

Bruce E. Kemp, Michael W. Parker, Shuhong Hu, Tony Tiganis, Colin House

Research output: Contribution to journalArticleResearchpeer-review

107 Citations (Scopus)

Abstract

Protein crystallography has revealed that protein kinases have extended 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 the extended substrate-binding groove, making multiple specific electrostatic and non-polar contacts. With masterly economy, Nature has exploited the active site in many protein kinases to both recognize substrates with great specificity and autoregulate by remaining inactive until the appropriate activation signal is received.

Original languageEnglish
Pages (from-to)440-444
Number of pages5
JournalTrends in Biochemical Sciences
Volume19
Issue number11
DOIs
Publication statusPublished - 1 Jan 1994
Externally publishedYes

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