5N9W

Structure of adenylation domain THR1 involved in the biosynthesis of 4-chlorothreonine in Streptomyces SP.OH-5093, apo structure

Replaces:  5APL

Summary for 5N9W

• Entry DOI: 10.2210/pdb5n9w/pdb
• Related: 5N9X
• Descriptor: Adenylation domain, ACETATE ION (3 entities in total)
• Functional Keywords: adenylation domain, substrate specificity, non-ribosomal code, transferase
• Biological source: Streptomyces sp.
• Total number of polymer chains: 2
• Total formula weight: 115627.01

Authors

Savino, C.,Vallone, B.,Scaglione, A.,Parisi, G.,Montemiglio, L.C.,Fullone, M.R.,Grgurina, I. (deposition date: 2017-02-27, release date: 2017-07-26, Last modification date: 2024-01-17)

Primary citation

Scaglione, A.,Fullone, M.R.,Montemiglio, L.C.,Parisi, G.,Zamparelli, C.,Vallone, B.,Savino, C.,Grgurina, I.
Structure of the adenylation domain Thr1 involved in the biosynthesis of 4-chlorothreonine in Streptomyces sp. OH-5093-protein flexibility and molecular bases of substrate specificity.
FEBS J., 284:2981-2999, 2017

PubMed Abstract: We determined the crystal structure of Thr1, the self-standing adenylation domain involved in the nonribosomal-like biosynthesis of free 4-chlorothreonine in Streptomyces sp. OH-5093. Thr1 shows two monomers in the crystallographic asymmetric unit with different relative orientations of the C- and N-terminal subdomains both in the presence of substrates and in the unliganded form. Cocrystallization with substrates, adenosine 5'-triphosphate and l-threonine, yielded one monomer containing the two substrates and the other in complex with l-threonine adenylate, locked in a postadenylation state. Steady-state kinetics showed that Thr1 activates l-Thr and its stereoisomers, as well as d-Ala, l- and d-Ser, albeit with lower efficiency. Modeling of these substrates in the active site highlighted the molecular bases of substrate discrimination. This work provides the first crystal structure of a threonine-activating adenylation enzyme, a contribution to the studies on conformational rearrangement in adenylation domains and on substrate recognition in nonribosomal biosynthesis.

PubMed: 28704585
DOI: 10.1111/febs.14163

Experimental method

X-RAY DIFFRACTION (2.456 Å)