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Sökning: WFRF:(Danielson U. Helena) > (2015-2019) > Unveiling the Bioch...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004207naa a2200373 4500
001oai:DiVA.org:uu-394688
003SwePub
008191024s2019 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3946882 URI
0247 a https://doi.org/10.1021/acs.biochem.9b004202 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Fabini, Edoardou Alma Mater Studiorum Univ Bologna, Dept Pharm & Biotechnol, Bologna, Italy;CNR, Natl Res Council, Inst Organ Synth & Photoreact ISOF, Bologna, Italy4 aut
2451 0a Unveiling the Biochemistry of the Epigenetic Regulator SMYD3
264 c 2019-08-07
264 1b AMER CHEMICAL SOC,c 2019
338 a print2 rdacarrier
520 a SET and MYND domain-containing protein 3 (SMYD3) is a lysine methyltransferase that plays a central role in a variety of cancer diseases, exerting its pro-oncogenic activity by methylation of key proteins, of both nuclear and cytoplasmic nature. However, the role of SMYD3 in the initiation and progression of cancer is not yet fully understood and further biochemical characterization is required to support the discovery of therapeutics targeting this enzyme. We have therefore developed robust protocols for production, handling, and crystallization of SMYD3 and biophysical and biochemical assays for clarification of SMYD3 biochemistry and identification of useful lead compounds. Specifically, a time-resolved biosensor assay was developed for kinetic characterization of SMYD3 interactions. Functional differences in SMYD3 interactions with its natural small molecule ligands SAM and SAH were revealed, with SAM forming a very stable complex. A variety of peptides mimicking putative substrates of SMYD3 were explored in order to expose structural features important for recognition. The interaction between SMYD3 and some peptides was influenced by SAM. A nonradioactive SMYD3 activity assay using liquid chromatography-mass spectrometry (LC-MS) analysis explored substrate features of importance also for methylation. Methylation was notable only toward MAP kinase kinase kinase 2 (MAP3K2_K-260)-mimicking peptides, although binary and tertiary complexes were detected also with other peptides. The analysis supported a random bi-bi mechanistic model for SMYD3 methyltransferase catalysis. Our work unveiled complexities in SMYD3 biochemistry and resulted in procedures suitable for further studies and identification of novel starting points for design of effective and specific leads for this potential oncology target.
650 7a NATURVETENSKAPx Biologix Biokemi och molekylärbiologi0 (SwePub)106022 hsv//swe
650 7a NATURAL SCIENCESx Biological Sciencesx Biochemistry and Molecular Biology0 (SwePub)106022 hsv//eng
7001 a Talibov, Vladimir O,d 1991-u Uppsala universitet,Biokemi4 aut0 (Swepub:uu)vlata700
7001 a Mihalic, Filipu Uppsala universitet,Institutionen för kemi - BMC4 aut0 (Swepub:uu)filmi699
7001 a Naldi, Marinau Alma Mater Studiorum Univ Bologna, Dept Pharm & Biotechnol, Bologna, Italy;St Orsola Marcello Malpighi Hosp, Ctr Appl Biomed Res CRBA, Bologna, Italy4 aut
7001 a Bartolini, Manuelau Alma Mater Studiorum Univ Bologna, Dept Pharm & Biotechnol, Bologna, Italy4 aut
7001 a Bertucci, Carlou Alma Mater Studiorum Univ Bologna, Dept Pharm & Biotechnol, Bologna, Italy4 aut
7001 a Del Rio, Albertou CNR, Natl Res Council, Inst Organ Synth & Photoreact ISOF, Bologna, Italy;Innovamol Consulting Srl, Modena, Italy4 aut
7001 a Danielson, U. Helena,c Professor,d 1959-u Uppsala universitet,Biokemi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)helenads
7102 a Alma Mater Studiorum Univ Bologna, Dept Pharm & Biotechnol, Bologna, Italy;CNR, Natl Res Council, Inst Organ Synth & Photoreact ISOF, Bologna, Italyb Biokemi4 org
7730 t Biochemistryd : AMER CHEMICAL SOCg 58:35, s. 3634-3645q 58:35<3634-3645x 0006-2960x 1520-4995
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-394688
8564 8u https://doi.org/10.1021/acs.biochem.9b00420

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