From owner-btk-mca@hgmp.mrc.ac.uk Thu Jun 28 10:37:27 2001 Return-Path: Received: from localhost (localhost [127.0.0.1]) by mercury.hgmp.mrc.ac.uk (Postfix) with ESMTP id 0BEA317A61 for ; Thu, 28 Jun 2001 10:37:20 +0100 (BST) Received: from localhost (localhost [127.0.0.1]) by mercury.hgmp.mrc.ac.uk (Postfix) with ESMTP id 265ED17AC9 for ; Thu, 28 Jun 2001 10:37:13 +0100 (BST) Received: from niobium.hgmp.mrc.ac.uk (niobium [193.62.192.41]) by mercury.hgmp.mrc.ac.uk (Postfix) with ESMTP id D427317ADB for ; Thu, 28 Jun 2001 10:37:05 +0100 (BST) Received: (from news@localhost) by niobium.hgmp.mrc.ac.uk (8.9.3+Sun/8.8.8) id KAA29626 for btk-mca-list@hgmp.mrc.ac.uk; Thu, 28 Jun 2001 10:27:37 +0100 (BST) X-Authentication-Warning: niobium.hgmp.mrc.ac.uk: news set sender to using -f From: dbk@aber.ac.uk ("Douglas Kell") X-Newsgroups: bionet.metabolic-reg Subject: Re: Enzymes!?! Date: 28 Jun 2001 10:27:36 +0100 Organization: BIOSCI/MRC Human Genome Mapping Project Resource Centre Lines: 55 Message-ID: <3B3B0687.22335.3D386F38@localhost> References: Mime-Version: 1.0 Content-Type: text/plain; charset=US-ASCII Content-Transfer-Encoding: 7BIT X-Complaints-To: news@net.bio.net X-Received: from localhost (localhost [127.0.0.1]) by mercury.hgmp.mrc.ac.uk (Postfix) with ESMTP id 7EF0A17ACD for ; Thu, 28 Jun 2001 10:27:33 +0100 (BST) X-Received: from braint.aber.ac.uk (braint.aber.ac.uk [144.124.16.42]) by mercury.hgmp.mrc.ac.uk (Postfix) with ESMTP id 7C84F17A79 for ; Thu, 28 Jun 2001 10:27:26 +0100 (BST) X-Received: from pcbdad.dbs.aber.ac.uk ([144.124.113.30] helo=aardvark) by braint.aber.ac.uk with esmtp (Exim 3.21 #1) id 15FY57-00086v-00; Thu, 28 Jun 2001 10:27:25 +0100 X-To: btk-mca@hgmp.mrc.ac.uk X-Reply-To: dbk@aber.ac.uk X-Cc: X-Priority: normal X-In-reply-to: X-Mailer: Pegasus Mail for Win32 (v3.12c) To: btk-mca@hgmp.mrc.ac.uk Sender: owner-btk-mca@hgmp.mrc.ac.uk Precedence: bulk I should know better than to respond to this...., but.... Transition state theory (TST) is not the only game in town so far as explaining 'how' enzymes work. In fact its chief assumption (a static energy barrier) is OBVIOUSLY untrue for the highly fluctuating things that enzymes are. The eponymous book edited by Rick Welch covers a lot of the early work pointing up alternatives The Fluctuating Enzyme (ed. Welch, G..R.), John Wiley, New York, 1986. If the role of a good theory is to have some predictive power as well (I am not sold on this; most often in science the competition between theories is actually on the basis of explaining EXISTING facts which the party line usually likes - or is forced - to ignore, and there are plenty fo precedents even in my own experience...) then theories that recognise the role of fluctuations give an obvious explanation for the (often substantial) effects of VISCOSITY on k-cat, which TST really has nothing to say about. Scrutton and Sutcliffe at Leicester review more modern alternative views based largely on tunnelling. Personally I think these types of ideas are right on the button, and that many new approaches that have recently become available to enzymologists will make it obvious that TST was a seductive but less than optimal way to think about enzyme catalysis. Scrutton, N. S., Basran, J. & Sutcliffe, M. J. (1999). New insights into enzyme catalysis - Ground state tunnelling driven by protein dynamics. European Journal of Biochemistry 264, 666-671. Scrutton, N. S. (1999). Enzymes in the quantum world. Biochemical Society Transactions 27, 767-779. Sutcliffe, M. J. & Scrutton, N. S. (2000). Enzyme catalysis: over-the- barrier or through-the-barrier? Trends in Biochemical Sciences 25, 405-408. Sutcliffe, M. J. & Scrutton, M. S. (2000). Enzymology takes a quantum leap forward. Philos. Trans. R. Soc. Lond. Ser. A-Math. Phys. Eng. Sci. 358, 367-386. This may liven up the newsgroup... All the best, Douglas. ******************************************************************** *(Prof.) Douglas B. Kell Phone: +44 1970 622334 * *Director of Research * *Institute of Biological Sciences Fax: +44 1970 622354 * *Cledwyn Building * *University of Wales, Email: dbk@aber.ac.uk * *Aberystwyth SY23 3DD, U.K. http://gepasi.dbs.aber.ac.uk/ * ******************************************************************** ******************************************************************** --- .