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Crystal structure of Scabin, a mono-ADP-ribosyltransferase from Streptomyces scabiesCrystal structure of Scabin, a mono-ADP-ribosyltransferase from Streptomyces scabies
Structural highlights
FunctionPublication Abstract from PubMedA bioinformatics strategy was used to identify Scabin, a novel DNA-targeting enzyme from the plant pathogen 87.22 strain of Streptomyces scabies. Scabin shares nearly 40% sequence identity with the Pierisin family of mono-ADP-ribosyltransferase toxins. Scabin was purified to homogeneity as a 22-kDa single-domain enzyme and was shown to possess high NAD+-glycohydrolase (KM(NAD) = 68 +/- 3 microM; kcat = 94 +/- 2 min-1) activity with an R-S-Q-X-E motif; it was also shown to target deoxyguanosine and showed sigmoidal enzyme kinetics (K0.5(deoxyguanosine) = 302 +/- 12 microM; kcat = 14 min-1). Mass spectrometry analysis revealed that Scabin labels the exocyclic amino group on guanine bases in either single-stranded or double-stranded DNA. Several small molecule inhibitors were identified and the most potent compounds were found to inhibit the enzyme activity with Ki values ranging from 3 to 24 microM. PJ34, a well-known inhibitor of poly-ADP-ribosyltransferases, was shown to be the most potent inhibitor of Scabin. Scabin was crystallized and it represents the first structure of a DNA-targeting mono-ADP-ribosyltransferase enzyme; the structures of the apo form (1.45A) and with two inhibitors (P6-E, 1.4A; PJ34, 1.6A) were solved. These structures are also the first high-resolution models of the Pierisin subgroup of the mono-ADP-ribosyltransferase toxin family. A model of Scabin with its DNA substrate is also proposed. Scabin, a novel DNA-acting ADP-ribosyltransferase from Streptomyces scabies.,Lyons B, Ravulapalli R, Lanoue J, Lugo MR, Dutta D, Carlin S, Merrill AR J Biol Chem. 2016 Mar 21. pii: jbc.M115.707653. PMID:27002155[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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