Not knowing more details about the enzyme, etc, makes this a little difficult. I would think you might need a more polarizing group nearby to shift the pKa. The first thing that jumps to mind for me is that the water molecule itself is what is activated in this case, making it nucleophilic. There is some precedence for this. Good luck and have fun with your structure!
Steve ________________________________ From: CCP4 bulletin board [mailto:[email protected]] On Behalf Of Deepak Oswal Sent: Monday, March 29, 2010 12:12 AM To: [email protected] Subject: [ccp4bb] activation of thiol group Dear colleagues: We have a 1.4 Angstrom structure of an enzyme showing a water molecule enclosed in a triangular pocket formed by the hydroxyl oxygens of 2 serine residues and a sulfhydryl group of an essential cysteine. The water molecule is forming a 2.8 Angstrom hydrogen bond with each of the hydroxyl groups of the 2 serines and a 2.9 Angstrom hydrogen bond with the sulfhydryl group of the cysteine. Is it possible for such a water molecule to lower the pKa of the cysteine and activate the thiol group? I would appreciate any comments or suggestions or information on any literature that I need to look up :> Sincerely, Deepak Notice: This e-mail message, together with any attachments, contains information of Merck & Co., Inc. (One Merck Drive, Whitehouse Station, New Jersey, USA 08889), and/or its affiliates Direct contact information for affiliates is available at http://www.merck.com/contact/contacts.html) that may be confidential, proprietary copyrighted and/or legally privileged. It is intended solely for the use of the individual or entity named on this message. If you are not the intended recipient, and have received this message in error, please notify us immediately by reply e-mail and then delete it from your system.
