6ZTU

Crystal structure of a cyclodipeptide synthase from Bacillus thermoamylovorans

Summary for 6ZTU

• Entry DOI: 10.2210/pdb6ztu/pdb
• Descriptor: Cyclodipeptide synthase, BtCDPS, (2S)-hexane-1,2-diol (3 entities in total)
• Functional Keywords: cdps, cyclodipeptide synthase, rna binding protein
• Biological source: Bacillus thermoamylovorans
• Total number of polymer chains: 1
• Total formula weight: 27379.58

Authors

Harding, C.J.,Czekster, C.M. (deposition date: 2020-07-20, release date: 2021-01-27, Last modification date: 2024-01-31)

Primary citation

Harding, C.J.,Sutherland, E.,Hanna, J.G.,Houston, D.R.,Czekster, C.M.
Bypassing the requirement for aminoacyl-tRNA by a cyclodipeptide synthase enzyme.
Rsc Chem Biol, 2:230-240, 2021

PubMed Abstract: Cyclodipeptide synthases (CDPSs) produce a variety of cyclic dipeptide products by utilising two aminoacylated tRNA substrates. We sought to investigate the minimal requirements for substrate usage in this class of enzymes as the relationship between CDPSs and their substrates remains elusive. Here, we investigated the enzyme, BtCDPS, which synthesises cyclo(l-Leu-l-Leu). We systematically tested where specificity arises and, in the process, uncovered small molecules (activated amino esters) that will suffice as substrates, although catalytically poor. We solved the structure of BtCDPS to 1.7 Å and combining crystallography, enzymatic assays and substrate docking experiments propose a model for how the minimal substrates interact with the enzyme. This work is the first report of a CDPS enzyme utilizing a molecule other than aa-tRNA as a substrate; providing insights into substrate requirements and setting the stage for the design of improved simpler substrates.

PubMed: 33937777
DOI: 10.1039/d0cb00142b

Experimental method

X-RAY DIFFRACTION (1.69 Å)