Adenylate-forming enzymes

Abstract

Thioesters, amides and esters are common chemical building blocks in a wide array of natural products. The formation of these bonds can be catalyzed in a variety of ways. For chemists, the use of an activating group is a common strategy and adenylate enzymes are exemplars of this approach. Adenylating enzymes activate the otherwise unreactive carboxylic acid by transforming the normal hydroxyl leaving group into adenosine monophosphate. Recently there have been a number of studies of such enzymes and in this review we suggest a new classification scheme. The review highlights the diversity in enzyme fold, active site architecture and metal coordination that has evolved to catalyze this particular reaction.

Crystal Structure of an Indole-3-Acetic Acid Amido Synthetase from Grapevine Involved in Auxin Homeostasis

“…The overall fold of the structure was similar to that of the At GH3-11 and At GH3-12 structures reported recently (Figures 2A, 2B, 3A, and 3B;Westfall et al, 2012) and of the adenylate-forming enzymes in general (reviewed in Gulick, 2009;Schmelz and Naismith, 2009). The N-terminal domain was an a/b fold with two separate b-structures (on either side of the inhibitor/catalytic site) each surrounded by a-helices ( Figure 1A).…”

“…The C-terminal domain of At GH3-12 undergoes a large change in conformation relative to the N-terminal domain during catalysis with a flexible region between the two domains acting as a hinge (Westfall et al, 2012). Such changes in conformation have been observed in other members of the large family of adenylating enzymes (reviewed in Gulick, 2009;Schmelz and Naismith, 2009). Due to the close structural similarities between the grapevine and Arabidopsis proteins, noted above, it can be predicted that the C-terminal domain of the grapevine GH3-1 enzyme also changes in conformation during catalysis.…”

“…Acyl-amido synthetases of the Gretchen Hagen3 (GH3) family comprise a group of plant-specific proteins with a role in hormone conjugation acting on auxins, jasmonic acid (JA), salicylic acid (SA), and benzoates (Staswick et al, 2002(Staswick et al, , 2005Okrent et al, 2009;Westfall et al, 2010). They are members of the ANL superfamily of adenylating enzymes, which are characterized by the employment of an adenylated reaction intermediate to attach organic acids to a variety of substrates (reviewed in Gulick, 2009;Schmelz and Naismith, 2009). The importance of GH3 proteins in plant development is indicated by the presence of families of these proteins throughout the plant kingdom, from mosses to flowering plants (Okrent and Wildermuth, 2011).…”

Structural basis of jasmonate-amido synthetase FIN219 in complex with glutathione S-transferase FIP1 during the JA signal regulation

“…The change from the closed form to the open form may occur in the presence of ATP, and this folding is the main conformation for the adenylate-forming reaction in the ANL (acyl-CoA synthetases, NRPS adenylation domains, and luciferase enzymes) superfamily of adenylating enzymes (42). Thioesterification is catalyzed when the enzyme changes back to the closed form, and the enzyme then completes a catalytic cycle and is available for the next reaction (10). Here, the FIP1-mediated new conformation of FIN219 provides another catalytic strategy, and this strategy is crucial for reciprocal cross-talk between FR light signaling and JA response (43).…”

“…The GH3 family in Arabidopsis is composed of 19 distinct proteins and is also conserved in plants such as rice (4)(5)(6), tomato (7,8), and maize (9), with 13, 15, and 13 members, respectively. Phylogenetically, the GH3 family is classified as part of the adenylate-forming enzyme superfamily, which contains proteins such as firefly luciferase-like enzymes (10). This diverse group of enzymes catalyzes the addition of AMP to carboxyl groups on a wide variety of substrates and typically contains three conserved motifs that form a binding pocket for ATP and AMP substrate intermediates (11).…”