User:Nicholas Bantz/Sandbox 1: Difference between revisions

The <scene name='81/811088/Swirmdomain/6'>SWIRM domain</scene> is seen in numerous enzymes that participate in histone binding and chromatin modification. The SWIRM domain of LSD-1 is 94 residues long and is comprised of an alpha-helix bundle <ref name="Stavropolous"/>. The longest helix, 𝛂C, separates the two other helix-turn-helix motifs, <scene name='81/811088/Swirmmotifs/4'>𝛂A/B and 𝛂D/E </scene><ref name="Stavropolous"/>. The SWIRM domain is associated with the oxidase domain via hydrophobic [https://en.wikipedia.org/wiki/Van_der_Waals_force van der Waals interactions] between <scene name='81/811088/Oxidaseandswirmchillin/4'>3 𝛂-helices in each domain</scene>: 𝛂A, 𝛂B, and 𝛂E motifs in the SWIRM domain and 𝛂A, 𝛂B, 𝛂M, motifs in the oxidase domain. The residues that create this hydrophobic interface (which spans nearly 1680 Ų) are practically invariant across histone-modifying proteins <ref name="Stavropolous"/>. The <scene name='81/811090/Hydrophobic_interface_new/1'> hydrophobic interface between the oxidase and SWIRM domains</scene> creates a cleft or tunnel that is also present in other chromatin modifying enzymes. This <scene name='81/811090/Hydrophobic_interface_new/3'>cleft</scene> is responsible for binding to DNA in the other enzymes through the presence of positively charged residues in the cleft <ref name="Stavropolous"/>. The SWIRM domain in LSD-1 is unique because the cleft that is formed by the hydrophobic SWIRM-oxidase interactions lacks the positively charged residues common in other enzymes <ref name="Stavropolous"/>. For this reason, it is proposed that the SWIRM cleft is used for binding of a histone tail (on the same histone as the substrate lysine) in order to hold the histone in place. Multiple experiments showed that mutations in hydrophobic residues that form the SWIRM-oxidase interface greatly reduced the catalytic activity of LSD-1 <ref name="Stavropolous"/>. This, and the proximity to the active site in the oxidase domain, exhibit the importance of the SWIRM cleft in the mechanism of LSD-1.