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==Crystal structure of Scabin, a mono-ADP-ribosyltransferase from Streptomyces scabies== | |||
<StructureSection load='5daz' size='340' side='right' caption='[[5daz]], [[Resolution|resolution]] 1.45Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5daz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DAZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DAZ FirstGlance]. <br> | |||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5daz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5daz OCA], [http://pdbe.org/5daz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5daz RCSB], [http://www.ebi.ac.uk/pdbsum/5daz PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A 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<ref>PMID:27002155</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5daz" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Dutta, D]] | |||
[[Category: Lanoue, J]] | [[Category: Lanoue, J]] | ||
[[Category: Merrill, A | [[Category: Merrill, A R]] | ||
[[Category: | [[Category: Apo-enzyme]] | ||
[[Category: Mono-adp-ribosyltransferase]] | |||
[[Category: Nad-binding protein]] | |||
[[Category: Transferase]] | |||
Revision as of 20:34, 10 May 2016
Crystal structure of Scabin, a mono-ADP-ribosyltransferase from Streptomyces scabiesCrystal structure of Scabin, a mono-ADP-ribosyltransferase from Streptomyces scabies
Structural highlights
Publication 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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