Journal:Protein Science:1: Difference between revisions

The ''Tc''AChE active site consists of two binding subsites. One of them is the "catalytic anionic site" (CAS), which involves the catalytic triad <scene name='Journal:Protein_Science:1/Cv/4'>Ser200, His440, and Glu327</scene> <font color='orange'><b>(colored orange)</b></font> and the conserved residues <scene name='2j3q/Active_site/3'>Trp84 and Phe330</scene> which also participate in ligand recognition. Another conserved residue <scene name='2j3q/Active_site/4'>Trp279</scene> <font color='cyan'><b>(colored cyan)</b></font> is situated at the second binding subsite, termed the "peripheral anionic site" (PAS), ~14 Å from CAS. <scene name='2j3q/Active_site/6'>Thioflavin T</scene> is a good example of the PAS-binding AChE inhibitors. <scene name='2j3q/Active_site/7'>Superposition</scene> of the crystal structure of the <font color='red'><b>edrophonium</b></font>/''Tc''AChE (mentioned above as a CAS-binding inhibitor) ([[2ack]]) on the <font color='magenta'><b>thioflavin T</b></font>/''Tc''AChE complex structure ([[2j3q]]) shows that these ligands' positions do not overlap. Of note is that Phe330, which is part of the CAS, is the single residue interacting with <font color='magenta'><b>thioflavin T</b></font>.  This residue is the only one which significantly <scene name='2j3q/Active_site/9'>changes its conformation</scene> to avoid clashes in comparison to other CAS residues of the <font color='red'><b>edrophonium</b></font>/''Tc''AChE complex <ref name="Ravelli">PMID:10089512</ref> <ref name="Sonoda">PMID:18512913</ref>.