Weber, T. & Marahiel, M.A. Exploring the domain structure of modular nonribosomal peptide synthetases.
We report herein the cloning, expression, and in vitro dimerizing activity of the chain-terminating TE domain of the modular PKS multienzyme that synthesizes the 16-membered diolide (1 b; Scheme 1) of elaiophylin,[ 2c, 15] a compound with antibacterial, antiviral, antifungal, and immunomodulatory activities.
In the simulations described, these patterns contain several modules of excited and inhibited domains, characteristic of modular architecture and spontaneous activity in the cortex [5], [6].
This sequential rearrangement sometimes necessitated changes in domain numbers (step 1) due to our view of domains being capable of modular rearrangement.
From an evolutionary standpoint, it is likely that the Spt6 SH2 domains provided the prototype for a family of modular domain for the phospho-specific interaction that have later evolved to be specific for phosphotyrosine.
For some proteins, this evolutionary consideration of modular domains could support alternative domain definitions (alternate evolutionary modules).
In another scheme, an SH2 domain may contain sequence motifs that are recognized by distinct types of modular domains.
Consequently, the benefits of modular domain rearrangements might be particularly pronounced, since the ability of modular evolution to swiftly implement changes to the protein repertoire may be a key process in both exploiting existing and creating functionalities.
The discovery of modular domains, such as the pleckstrin homology (PH) domains, able to interact with 3′-phosphorylated lipids marked a significant step forward in understanding the PI3K pathway 10– 12 The most significant example of PtdIns 3,4,5 P3-dependent PtdIns 3,4,5 P3-dependentt of serine/threonine-sprotein protein kinactivation).
We discuss the phosphopeptide binding of modular domains in DNA damage responses, FHA and BRCT, the smallest modular domain WW and the tyrosine kinase binding domain, such as Cbl TKB that recognizes phosphotyrosine.
