5v3h
From Proteopedia
(Difference between revisions)
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==Crystal structure of SMYD2 with SAM and EPZ033294== | ==Crystal structure of SMYD2 with SAM and EPZ033294== | ||
| - | <StructureSection load='5v3h' size='340' side='right' caption='[[5v3h]], [[Resolution|resolution]] 2.69Å' scene=''> | + | <StructureSection load='5v3h' size='340' side='right'caption='[[5v3h]], [[Resolution|resolution]] 2.69Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5v3h]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V3H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V3H FirstGlance]. <br> | <table><tr><td colspan='2'>[[5v3h]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V3H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V3H FirstGlance]. <br> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/SMYD2_HUMAN SMYD2_HUMAN]] Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins. Specifically methylates histone H3 'Lys-4' (H3K4me) and dimethylates histone H3 'Lys-36' (H3K36me2). Has also methyltransferase activity toward non-histone proteins such as p53/TP53 and RB1. Monomethylates 'Lys-370' of p53/TP53, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity of p53/TP53. Monomethylates 'Lys-860' of RB1/RB.<ref>PMID:17108971</ref> <ref>PMID:17805299</ref> <ref>PMID:18065756</ref> <ref>PMID:20870719</ref> | [[http://www.uniprot.org/uniprot/SMYD2_HUMAN SMYD2_HUMAN]] Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins. Specifically methylates histone H3 'Lys-4' (H3K4me) and dimethylates histone H3 'Lys-36' (H3K36me2). Has also methyltransferase activity toward non-histone proteins such as p53/TP53 and RB1. Monomethylates 'Lys-370' of p53/TP53, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity of p53/TP53. Monomethylates 'Lys-860' of RB1/RB.<ref>PMID:17108971</ref> <ref>PMID:17805299</ref> <ref>PMID:18065756</ref> <ref>PMID:20870719</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A key challenge in the development of precision medicine is defining the phenotypic consequences of pharmacological modulation of specific target macromolecules. To address this issue, a variety of genetic, molecular and chemical tools can be used. All of these approaches can produce misleading results if the specificity of the tools is not well understood and the proper controls are not performed. In this paper we illustrate these general themes by providing detailed studies of small molecule inhibitors of the enzymatic activity of two members of the SMYD branch of the protein lysine methyltransferases, SMYD2 and SMYD3. We show that tool compounds as well as CRISPR/Cas9 fail to reproduce many of the cell proliferation findings associated with SMYD2 and SMYD3 inhibition previously obtained with RNAi based approaches and with early stage chemical probes. | ||
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| + | Small molecule inhibitors and CRISPR/Cas9 mutagenesis demonstrate that SMYD2 and SMYD3 activity are dispensable for autonomous cancer cell proliferation.,Thomenius MJ, Totman J, Harvey D, Mitchell LH, Riera TV, Cosmopoulos K, Grassian AR, Klaus C, Foley M, Admirand EA, Jahic H, Majer C, Wigle T, Jacques SL, Gureasko J, Brach D, Lingaraj T, West K, Smith S, Rioux N, Waters NJ, Tang C, Raimondi A, Munchhof M, Mills JE, Ribich S, Porter Scott M, Kuntz KW, Janzen WP, Moyer M, Smith JJ, Chesworth R, Copeland RA, Boriack-Sjodin PA PLoS One. 2018 Jun 1;13(6):e0197372. doi: 10.1371/journal.pone.0197372., eCollection 2018. PMID:29856759<ref>PMID:29856759</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5v3h" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Histone methyltransferase|Histone methyltransferase]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Boriack-Sjodin, P A]] | [[Category: Boriack-Sjodin, P A]] | ||
[[Category: Protein lysine methyltransferase]] | [[Category: Protein lysine methyltransferase]] | ||
[[Category: Protein-inhibitor complex]] | [[Category: Protein-inhibitor complex]] | ||
[[Category: Transferase-transferase inhibitor complex]] | [[Category: Transferase-transferase inhibitor complex]] | ||
Revision as of 13:20, 10 May 2019
Crystal structure of SMYD2 with SAM and EPZ033294
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