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Front. Plant Sci. | doi: 10.3389/fpls.2019.00555

Spermidine synthase (SPDS) undergoes concerted structural rearrangements upon ligand binding – a case study of the two SPDS isoforms from Arabidopsis thaliana

 Bartosz Sekula1* and Zbigniew Dauter1
  • 1Synchrotron Radiation Research Section, Macromolecular Crystallography Laboratory, National Cancer Institute, United States

Spermidine synthases (SPDSs) catalyze the production of the linear triamine, spermidine, from putrescine. They utilize decarboxylated S-adenosylmethionine (dc-SAM), a universal cofactor of aminopropyltransferases, as a donor of the aminopropyl moiety. In this work, we describe crystal structures of two isoforms of SPDS from Arabidopsis thaliana (AtSPDS1 and AtSPDS2). AtSPDS1 and AtSPDS2 are dimeric enzymes that share the fold of the polyamine biosynthesis proteins. Subunits of both isoforms present the characteristic two-domain structure. Smaller, N-terminal domain is built of the two β-sheets, while the C-terminal domain has a Rossmann fold-like topology. The catalytic cleft composed of two main compartments, the dc-SAM binding site and the polyamine groove, is created independently in each AtSPDS subunits at the domain interface. We also provide the structural details about the dc-SAM binding mode and the inhibition of SPDS by a potent competitive inhibitor, cyclohexylamine (CHA). CHA occupies the polyamine binding site of AtSPDS where it is bound at the bottom of the active site analogically to the substrate. The crystallographic snapshots show in detail the structural rearrangements of AtSPDS1 and AtSPDS2 that are required to stabilize ligands within the active site. The concerted movements are observed in both compartments of the catalytic cleft, where three major parts significantly change their conformation. These are, (i) close to the glycine-rich region where aminopropyl moiety of dc-SAM is bound, (ii) the very flexible gate region with helix η6, which interacts with both, the adenine moiety of dc-SAM and the bound polyamine or inhibitor, and (iii) the N-terminal β-hairpin, that limits the putrescine binding grove at the bottom.

Keywords: polyamine biosynthesis, Spermine, Triamine, Spermidine, Putrescine, decarboxylated S-adenosylmethionine, Cyclohexylamine, aminopropyltransferase

Received: 05 Mar 2019; Accepted: 11 Apr 2019.

Edited by:

Antonio F. Tiburcio, University of Barcelona, Spain

Reviewed by:

Miguel A. Blazquez, Spanish National Research Council (CSIC), Spain
Taku Takahashi, Okayama University, Japan  

Copyright: © 2019 Sekula and Dauter. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Bartosz Sekula, Synchrotron Radiation Research Section, Macromolecular Crystallography Laboratory, National Cancer Institute, Argonne, Illinois, United States, bartosz.sekula@nih.gov