User:Madeleine Wilson/Sandbox 1: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 16: | Line 16: | ||
The secondary structure is composed of 10% <scene name='81/811086/Helices/3'>helices</scene> and 37% <scene name='81/811086/Beta_sheets/3'>beta sheets</scene>. The helical composition includes 3 <scene name='81/811086/Alpha_helices/4'>alpha helices</scene>, with two residing in the SET domain and one in the C-terminal domain. The alpha helices in the SET domain are two turns while the C-terminal helix is by far the largest with 4 turns. There are also 2 <scene name='81/811086/3-10_helices/4'>3-10 helices</scene> in the SET domain which are each one turn. There are 21 total beta strands which reside in the N-terminal domain and the SET domain. The beta strands are primarily anti-parallel and multiple antiparallel strands are connected by <scene name='81/811086/Type_i_beta_turns/3'>Type I</scene> and <scene name='81/811086/Type_ii_beta_turns/2'>Type II</scene> beta turns. | The secondary structure is composed of 10% <scene name='81/811086/Helices/3'>helices</scene> and 37% <scene name='81/811086/Beta_sheets/3'>beta sheets</scene>. The helical composition includes 3 <scene name='81/811086/Alpha_helices/4'>alpha helices</scene>, with two residing in the SET domain and one in the C-terminal domain. The alpha helices in the SET domain are two turns while the C-terminal helix is by far the largest with 4 turns. There are also 2 <scene name='81/811086/3-10_helices/4'>3-10 helices</scene> in the SET domain which are each one turn. There are 21 total beta strands which reside in the N-terminal domain and the SET domain. The beta strands are primarily anti-parallel and multiple antiparallel strands are connected by <scene name='81/811086/Type_i_beta_turns/3'>Type I</scene> and <scene name='81/811086/Type_ii_beta_turns/2'>Type II</scene> beta turns. | ||
===The Active Site=== | ===The Active Site=== | ||
| Line 31: | Line 27: | ||
The C-terminal domain of lysine methyltransferase is very important for the catalytic activity of the enzyme. The structures of the <scene name='81/811091/C_terminal_domain/1'>C-terminal domain (residues 345-366)</scene> serve the role of stabilizing the structures in the <scene name='81/811091/C_terminal_domain/16'>SET7 domain (residues 193-344)</scene> in the correct orientation for a reaction in the active site.<ref name="Xiao" /> Hydrophobic interactions in the C-terminal domain are mainly responsible for stabilizing the access channel for the lysine methylation site on histone H3. Residues 337-349 create a beta-hairpin structure that stabilizes the orientation of two tyrosine residues, Tyr335 and Tyr337, that form the opening to the lysine access channel. Furthermore, the hydrophobic packing of alpha-helix 3 against beta-sheet 19, specifically <scene name='81/811091/C_terminal_domain/13'>residues Leu357 and Phe 299</scene>, stabilize the orientation of the <scene name='81/811091/C_terminal_domain/14'>SAM cofactor</scene> so that its methyl donating group is oriented toward the lysine access channel. The orientation of the SAM cofactor is further stabilized with its hydrophobic interactions with C-terminal domain residues <scene name='81/811091/C_terminal_domain/18'>Trp352 and Glu356</scene>. <ref name="Xiao" /> | The C-terminal domain of lysine methyltransferase is very important for the catalytic activity of the enzyme. The structures of the <scene name='81/811091/C_terminal_domain/1'>C-terminal domain (residues 345-366)</scene> serve the role of stabilizing the structures in the <scene name='81/811091/C_terminal_domain/16'>SET7 domain (residues 193-344)</scene> in the correct orientation for a reaction in the active site.<ref name="Xiao" /> Hydrophobic interactions in the C-terminal domain are mainly responsible for stabilizing the access channel for the lysine methylation site on histone H3. Residues 337-349 create a beta-hairpin structure that stabilizes the orientation of two tyrosine residues, Tyr335 and Tyr337, that form the opening to the lysine access channel. Furthermore, the hydrophobic packing of alpha-helix 3 against beta-sheet 19, specifically <scene name='81/811091/C_terminal_domain/13'>residues Leu357 and Phe 299</scene>, stabilize the orientation of the <scene name='81/811091/C_terminal_domain/14'>SAM cofactor</scene> so that its methyl donating group is oriented toward the lysine access channel. The orientation of the SAM cofactor is further stabilized with its hydrophobic interactions with C-terminal domain residues <scene name='81/811091/C_terminal_domain/18'>Trp352 and Glu356</scene>. <ref name="Xiao" /> | ||
===The N-terminal Domain=== | |||
[[Image:Clustal.png|200px|right|thumb|Figure 1. Clustal alignment of N-terminals]] | |||
The N-terminal domain has no notable function in regard to the activity of KMT; in addition to this, no recent studies have been conducted to discover what the exact function of this region is. As this is a highly conserved region across species, it may be hypothesized this domain plays an integral part in stability. | |||
==Inhibitors== | ==Inhibitors== | ||
