ChickenHawk 0 Posted February 21, 2002 Acetylcholinesterase is a serine hydrolase that belongs to the esterase family within higher eukaryotes. This family acts on different types of carboxylic esters. Acetylcholinesterase's biological role is the termination of impulse transmissions at cholinergic synapses within the nervous system by rapid hydrolysis of the neurotransmitter, acetylcholine Acetylcholinesterase is an ellipsoidal molecule approximately 45 x 60 x 65 angstroms, which consists of a 12 stranded central mixed beta sheet surrounded by 14 alpha helices (Sussman et al, 1991). Studies have indicated several major domains within the protein: a catalytic active site composed of two subsites, the aromatic gorge in which the catalytic active site lies, and a peripheral anionic site, distinct from the catalytic active site, which plays a role in the confirmation of the residues within the aromatic gorge and active site. This view of the protein is provided for easier viewing of the 3-D structure of the entire protein in stereo. The active site is composed of two subsites: the esteratic subsite which contains the catalytic triad, and the anionic subsite that accommodates the positive quaternary pole of acetylcholine. The esteratic subsite contains the catalytic machinery of the enzyme: a catalytic triad of Ser 200, His 440, and Glu 327. This catalytic triad is similar to other serine proteases, except that this triad is the first to show Glu as the third member as opposed to Asp. In addition, the triad is of opposite handedness to that of the other proteases. The anionic subsite is defined by Trp 84, Phe 330, and Phe 331. Its role is to orient the charged part of the substrate that enters the active center. This role is the main function of the Trp residue (Sussman et al, 1991). This subsite has another interesting characteristic; it is involved in a "cross-talk" mechanism with the peripheral anionic site which will be discussed later. The aromatic gorge in the protein is approximately 20 angstroms deep and penetrates halfway into the enzyme. The active site lies at the base of this gorge only 4 angstroms above the base, leading some to label this the active gorge. The aromatic gorge is a more appropriate term, though, because 40% of its lining is composed of 14 aromatic residues which are highly conserved from different species of acetylcholinesterases (Harel et al, 1993). The high aromatic content of the walls and floor may explain why studies have proposed hydrophobic and anionic binding sites independent of the active site. Only a few acidic residues are present within the gorge. The most interesting aspect of this enzyme is the peripheral anionic site (PAS) on its surface. Site-directed labeling and mutagenesis studies place the location of the PAS at or near the rim of the aromatic gorge (Barak et al, 1994). This site has the ability to bind to many different types of ligands, and by doing so effects the conformation of the active center. Six residues have established activity within this site: Trp 286, Tyr 72, Tyr 124, Glu 285, and Asp 74 and Tyr 341, which are located on the opposite side of the gorge entrance to the previous four. This array of residues exhibits flexibility which accommodates many distinct ligands, and also implies their conformational mobility (Ordentlich et al, 1993). The common feature of these conformations is a core comprised of Trp 286 and Asp 74. As mentioned above, the peripheral anionic site is involved in a "cross-talk" mechanism with the active site. This mechanism is an interaction between the Trp 286 and Trp 86 residues. When Trp 286 is bonded on the periphery, it effects the Trp 86 in the active site and causes distinct conformations of the active site to occur, thus changing the functionality of the enzyme. Asp 74 also plays a role in allosteric modulation of the enzyme. This residue acts with Tyr 341, as well as other residues along the aromatic gorge, and terminates at Tyr 337. The sensitivity of these residues and the plasticity of the active center are probably the result of evolutionary design aimed to confer optimal catalytic activity under a wide variety of conditions that are characteristic for the operation of acetylcholinesterase in the synaptic cleft. Share this post Link to post Share on other sites
Damage Inc 0 Posted February 21, 2002 I have a small word for this whole text: spam. Share this post Link to post Share on other sites
ChickenHawk 0 Posted February 21, 2002 It looks good though. Share this post Link to post Share on other sites
Damage Inc 0 Posted February 21, 2002 You just copied thehamster's idea of having spam that looks good Share this post Link to post Share on other sites
Guest Posted February 21, 2002 </span><table border="0" align="center" width="95%" cellpadding="3" cellspacing="1"><tr><td>Quote </td></tr><tr><td id="QUOTE">It looks good though.<span id='postcolor'> Ok but wtf is it. Share this post Link to post Share on other sites
Thehamster 0 Posted February 21, 2002 Look goodlooking spam is my idea if you want to use you pay me in gold wood chippings. Share this post Link to post Share on other sites
madmike 0 Posted February 21, 2002 Hey Hamster, have you started working in a wood yard or for a loggin company. Maybe even B&Q? Share this post Link to post Share on other sites
Fenna 0 Posted February 21, 2002 You can do it if you B & Q it. Share this post Link to post Share on other sites
Thehamster 0 Posted February 21, 2002 </span><table border="0" align="center" width="95%" cellpadding="3" cellspacing="1"><tr><td>Quote (madmike @ Feb. 20 2002,18:57)</td></tr><tr><td id="QUOTE">Hey Hamster, have you started working in a wood yard or for a loggin company. Maybe even B&Q?<span id='postcolor'> Don't need I got my own logging company Share this post Link to post Share on other sites
madmike 0 Posted February 21, 2002 What in flashpoint? Share this post Link to post Share on other sites
nordin dk 0 Posted February 21, 2002 Now I'm tempted to write a lot that noone understands. How about a small thing concerning Kindertotenlieder and Mahler's concerns about his own mortality. Anyone interested? Share this post Link to post Share on other sites
nordin dk 0 Posted February 21, 2002 Should I make it a new topic of it's own, or just continue this one? Share this post Link to post Share on other sites
Thehamster 0 Posted February 21, 2002 Yep I wanna know. Share this post Link to post Share on other sites
Damage Inc 0 Posted February 21, 2002 Me too I'm always interested in stuff that I don't understand. Share this post Link to post Share on other sites
Thehamster 0 Posted February 21, 2002 </span><table border="0" align="center" width="95%" cellpadding="3" cellspacing="1"><tr><td>Quote (nordin dk @ Feb. 20 2002,19:37)</td></tr><tr><td id="QUOTE">Should I make it a new topic of it's own, or just continue this one?<span id='postcolor'> Just stick it in here. Share this post Link to post Share on other sites
nordin dk 0 Posted February 21, 2002 Well to get the discussion going, you all know the various theoris put forth claiming that Mahler in writing Der Kindertotenlider actually foresaw the death of his own daughter, right? Share this post Link to post Share on other sites
nordin dk 0 Posted February 21, 2002 Now surely you must know this. This is bread-&-butter stuff! Share this post Link to post Share on other sites
Thehamster 0 Posted February 21, 2002 Ummmmmmmmm I don't like bread and butter stuff. I'm a more of a fountain of knowledge type guy. Share this post Link to post Share on other sites
nordin dk 0 Posted February 21, 2002 How about the occasional drip-of-aha ? Share this post Link to post Share on other sites
Thehamster 0 Posted February 21, 2002 aaa the occasional drip-of-aha now your talking my language. Share this post Link to post Share on other sites
Oligo 1 Posted February 22, 2002 It's quite sad that I'm probably the only one in here who understood everything said in the first post. It's not spam to me. Share this post Link to post Share on other sites
nordin dk 0 Posted February 22, 2002 Nothing is spam to some people here Share this post Link to post Share on other sites
