5OO5

Streptomyces PAC13 with uridine uronic acid

Summary for 5OO5

• Entry DOI: 10.2210/pdb5oo5/pdb
• Descriptor: Putative cupin_2 domain-containing isomerase, uridine uronic acid (3 entities in total)
• Functional Keywords: pac13, dehydratase, pacidamycin, biosynthetic protein
• Biological source: Streptomyces coeruleorubidus
• Total number of polymer chains: 1
• Total formula weight: 14369.80

Authors

Chung, C.,Michailidou, F. (deposition date: 2017-08-05, release date: 2017-08-23, Last modification date: 2024-05-08)

Primary citation

Michailidou, F.,Chung, C.W.,Brown, M.J.B.,Bent, A.F.,Naismith, J.H.,Leavens, W.J.,Lynn, S.M.,Sharma, S.V.,Goss, R.J.M.
Pac13 is a Small, Monomeric Dehydratase that Mediates the Formation of the 3'-Deoxy Nucleoside of Pacidamycins.
Angew. Chem. Int. Ed. Engl., 56:12492-12497, 2017

PubMed Abstract: The uridyl peptide antibiotics (UPAs), of which pacidamycin is a member, have a clinically unexploited mode of action and an unusual assembly. Perhaps the most striking feature of these molecules is the biosynthetically unique 3'-deoxyuridine that they share. This moiety is generated by an unusual, small and monomeric dehydratase, Pac13, which catalyses the dehydration of uridine-5'-aldehyde. Here we report the structural characterisation of Pac13 with a series of ligands, and gain insight into the enzyme's mechanism demonstrating that H42 is critical to the enzyme's activity and that the reaction is likely to proceed via an E1cB mechanism. The resemblance of the 3'-deoxy pacidamycin moiety with the synthetic anti-retrovirals, presents a potential opportunity for the utilisation of Pac13 in the biocatalytic generation of antiviral compounds.

PubMed: 28786545
DOI: 10.1002/anie.201705639

Experimental method

X-RAY DIFFRACTION (1.78 Å)