User:Nicholas Bantz/Sandbox 1: Difference between revisions

The <scene name='81/811088/Towerdomain/5'>tower domain</scene> is a 100 residue protrusion off of the main protein body of LSD-1, comprised of 2 right-handed [https://en.wikipedia.org/wiki/Alpha_helix-helices 𝛂-helices]. The longer helix, T𝛂A, is an LSD-1 specific element that has not been found in any other oxidase proteins <ref name="Stavropolous"/>. The shorter helix, T𝛂B, is positioned near the active site of the oxidase domain. T𝛂B connects directly to helix 𝛂D of the oxidase domain through a highly conserved connector loop. The exact function of the tower domain is not known, but it is proposed to regulate the size of the active site chamber through this <scene name='81/811090/Tb-dinteraction/2'>TαB-αD interaction</scene>. The T𝛂B-𝛂D interaction is responsible for the proper positioning of <scene name='81/811090/Phe538-tyr761interaction/2'>Phe538</scene>, a side chain of 𝛂D that is located in the catalytic chamber, for proper recognition and binding of the substrate lysine through hydrophobic interactions. In addition, the T𝛂B-𝛂D interaction positions 𝛂D in the correct manner to provide [https://en.wikipedia.org/wiki/Hydrogen_bond hydrogen bonding] to <scene name='81/811090/Phe538-tyr761interaction/3'>Tyr761</scene>. Tyr761 is positioned in the catalytic chamber next to the FAD cofactor and aids in the binding of the lysine substrate <ref name="Stavropolous"/>. Therefore, the base of the tower domain forms a direct connection to the oxidase domain and plays a crucial role in the shape and catalytic activity of the active site. In fact, removing the tower domain via a mutation resulted in a drastic decrease in catalytic efficiency <ref name="Stavropolous"/>.  The tower domain has also been found to interact with other proteins and complexes, such as CoREST (Figure 2), as a switch to allosterically regulate the catalytic activity of the protein<ref name="Yang">doi: 10.1016/j.molcel.2006.07.012</ref>.  Overall, the exact function of the tower domain has not yet been fully determined, but it is known to be vital to the catalytic activity of LSD-1.