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Structure and function of SET and MYND domain-containing proteins.

Spellmon N, Holcomb J, Trescott L, Sirinupong N, Yang Z - Int J Mol Sci (2015)

Bottom Line: SET (Suppressor of variegation, Enhancer of Zeste, Trithorax) and MYND (Myeloid-Nervy-DEAF1) domain-containing proteins (SMYD) have been found to methylate a variety of histone and non-histone targets which contribute to their various roles in cell regulation including chromatin remodeling, transcription, signal transduction, and cell cycle control.During early development, SMYD proteins are believed to act as an epigenetic regulator for myogenesis and cardiomyocyte differentiation as they are abundantly expressed in cardiac and skeletal muscle.This review will examine the biological relevance and gather all of the current structural data of SMYD proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, 540 East Canfield Street, Detroit, MI 48201, USA. nicholas.spellmon@wayne.edu.

ABSTRACT
SET (Suppressor of variegation, Enhancer of Zeste, Trithorax) and MYND (Myeloid-Nervy-DEAF1) domain-containing proteins (SMYD) have been found to methylate a variety of histone and non-histone targets which contribute to their various roles in cell regulation including chromatin remodeling, transcription, signal transduction, and cell cycle control. During early development, SMYD proteins are believed to act as an epigenetic regulator for myogenesis and cardiomyocyte differentiation as they are abundantly expressed in cardiac and skeletal muscle. SMYD proteins are also of therapeutic interest due to the growing list of carcinomas and cardiovascular diseases linked to SMYD overexpression or dysfunction making them a putative target for drug intervention. This review will examine the biological relevance and gather all of the current structural data of SMYD proteins.

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Related in: MedlinePlus

Additional substrate binding site. (A) Surface representation of the PEG binding site in SMYD2. PEG is depicted by sticks with the carbon atoms colored in purple. ERα peptide is displayed as ribbon and colored yellow; (B) Putative PEG interacting residues. SMYD2 residues are colored according to domains. ERα residues are shown in yellow. PEG is represented in the same way as in (A); and (C) Comparison of the binding sites of ERα (yellow), p53 (blue), PEG (purple), Hsp90 (light blue), and a ribosomal peptide (orange). The ribosomal peptide is overlaid with 2Fo−Fc omit map calculated at 2.8 Å and contoured at 1.5σ. The Hsp90 peptide is modeled by superposition of the SMYD2 CTD and Hop1 TPR.
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ijms-16-01406-f007: Additional substrate binding site. (A) Surface representation of the PEG binding site in SMYD2. PEG is depicted by sticks with the carbon atoms colored in purple. ERα peptide is displayed as ribbon and colored yellow; (B) Putative PEG interacting residues. SMYD2 residues are colored according to domains. ERα residues are shown in yellow. PEG is represented in the same way as in (A); and (C) Comparison of the binding sites of ERα (yellow), p53 (blue), PEG (purple), Hsp90 (light blue), and a ribosomal peptide (orange). The ribosomal peptide is overlaid with 2Fo−Fc omit map calculated at 2.8 Å and contoured at 1.5σ. The Hsp90 peptide is modeled by superposition of the SMYD2 CTD and Hop1 TPR.

Mentions: The polyethylene glycol (PEG)-binding site found in the SMYD2–ERα structure has suggested additional and extended substrate-binding pockets (Figure 7A) [32]. PEG binding was also found in other protein structures, and in most cases, PEG binding has important functional implications mimicking ligand binding in proteins [52,53,54]. In SMYD2, the PEG molecule primarily binds to the CTD domain with an omega-turn conformation with one end found near the surface groove shaped by αH, αI, and αJ and the other end extended between αK and αL helices (Figure 7B). The residues responsible for contributing PEG binding include Lys309, Tyr344, Gln345, Gly348, Leu351, Tyr352, Trp356, and Lys387 from the CTD and Glu190 from the SET domain. The ERα peptide may also interact and stabilize PEG binding due to its close proximity to Arg+3. Note that all of the residues participating in PEG binding (except for Lys309) are not conserved in the SMYD family, which indicates a possible SMYD2-specific binding site.


Structure and function of SET and MYND domain-containing proteins.

Spellmon N, Holcomb J, Trescott L, Sirinupong N, Yang Z - Int J Mol Sci (2015)

Additional substrate binding site. (A) Surface representation of the PEG binding site in SMYD2. PEG is depicted by sticks with the carbon atoms colored in purple. ERα peptide is displayed as ribbon and colored yellow; (B) Putative PEG interacting residues. SMYD2 residues are colored according to domains. ERα residues are shown in yellow. PEG is represented in the same way as in (A); and (C) Comparison of the binding sites of ERα (yellow), p53 (blue), PEG (purple), Hsp90 (light blue), and a ribosomal peptide (orange). The ribosomal peptide is overlaid with 2Fo−Fc omit map calculated at 2.8 Å and contoured at 1.5σ. The Hsp90 peptide is modeled by superposition of the SMYD2 CTD and Hop1 TPR.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307310&req=5

ijms-16-01406-f007: Additional substrate binding site. (A) Surface representation of the PEG binding site in SMYD2. PEG is depicted by sticks with the carbon atoms colored in purple. ERα peptide is displayed as ribbon and colored yellow; (B) Putative PEG interacting residues. SMYD2 residues are colored according to domains. ERα residues are shown in yellow. PEG is represented in the same way as in (A); and (C) Comparison of the binding sites of ERα (yellow), p53 (blue), PEG (purple), Hsp90 (light blue), and a ribosomal peptide (orange). The ribosomal peptide is overlaid with 2Fo−Fc omit map calculated at 2.8 Å and contoured at 1.5σ. The Hsp90 peptide is modeled by superposition of the SMYD2 CTD and Hop1 TPR.
Mentions: The polyethylene glycol (PEG)-binding site found in the SMYD2–ERα structure has suggested additional and extended substrate-binding pockets (Figure 7A) [32]. PEG binding was also found in other protein structures, and in most cases, PEG binding has important functional implications mimicking ligand binding in proteins [52,53,54]. In SMYD2, the PEG molecule primarily binds to the CTD domain with an omega-turn conformation with one end found near the surface groove shaped by αH, αI, and αJ and the other end extended between αK and αL helices (Figure 7B). The residues responsible for contributing PEG binding include Lys309, Tyr344, Gln345, Gly348, Leu351, Tyr352, Trp356, and Lys387 from the CTD and Glu190 from the SET domain. The ERα peptide may also interact and stabilize PEG binding due to its close proximity to Arg+3. Note that all of the residues participating in PEG binding (except for Lys309) are not conserved in the SMYD family, which indicates a possible SMYD2-specific binding site.

Bottom Line: SET (Suppressor of variegation, Enhancer of Zeste, Trithorax) and MYND (Myeloid-Nervy-DEAF1) domain-containing proteins (SMYD) have been found to methylate a variety of histone and non-histone targets which contribute to their various roles in cell regulation including chromatin remodeling, transcription, signal transduction, and cell cycle control.During early development, SMYD proteins are believed to act as an epigenetic regulator for myogenesis and cardiomyocyte differentiation as they are abundantly expressed in cardiac and skeletal muscle.This review will examine the biological relevance and gather all of the current structural data of SMYD proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, 540 East Canfield Street, Detroit, MI 48201, USA. nicholas.spellmon@wayne.edu.

ABSTRACT
SET (Suppressor of variegation, Enhancer of Zeste, Trithorax) and MYND (Myeloid-Nervy-DEAF1) domain-containing proteins (SMYD) have been found to methylate a variety of histone and non-histone targets which contribute to their various roles in cell regulation including chromatin remodeling, transcription, signal transduction, and cell cycle control. During early development, SMYD proteins are believed to act as an epigenetic regulator for myogenesis and cardiomyocyte differentiation as they are abundantly expressed in cardiac and skeletal muscle. SMYD proteins are also of therapeutic interest due to the growing list of carcinomas and cardiovascular diseases linked to SMYD overexpression or dysfunction making them a putative target for drug intervention. This review will examine the biological relevance and gather all of the current structural data of SMYD proteins.

Show MeSH
Related in: MedlinePlus