Enzyme "lock and key" is still being used or there is another system replaced it?

Question

argued with my teacher so i really need this answer

Answer 1

Lock and key is a gloss, and your intution is very correct there is more to enzymatic catalysis than simply fiting the substrate into the active site of the enzyme.

In graduate school we talk about docking, packing, conformational fit, or binding energies rather than using a lock and key analogy. Certainly how a substrate fits into the active site of an enzyme is essential to the function of the enzyme, the key fitting to the lock as it were. However in almost all cases there is more involved in catalysis than simply fiting the substrate into the enzyme.

This is a big field, first the short answer:

Easily the most readable and accessible information is at David S. Goodsell's Molecule of the month:
http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/alphabetical_list.html

For more substantial details about enzyme catalysis.

Dr. Ziegler's notes are really excelent
http://www.biochem.arizona.edu/classes/bioc462/462a/NOTES/ENZYMES/enzyme_mechanism.html

When he talks about binding energies really he talking about "the lock and key", how well the substare fits into the active site of the enzyme. He provides one example Hexokinase of an enzyme where the mechanism is entirely one of conformational fit. i.e. where the reaction is facilitated purley by binding the two substrates in close proximity.

He goes on to say: "The rest of these catalytic mechanisms are more specific, involving properly positioned catalytic groups on the enzyme that aid in bond cleavage and formation."

And he goes into some detail on the Serine proteases ( which get over worked as examples in this subject.) However for any of the serine proteases ( Trypsin, Chymotrypsin, Elastase) if you mutate the serine to say a glycine or valine you will get an inactive enzyme,despite the fact that the subsrate still binds quite well into the active site.

Enzyme Mechanisms by Wilbur Campbell at
http://www.bio.mtu.edu/campbell/401lec15all.pdf
http://www.bio.mtu.edu/campbell/401lec15ball.pdf
is another very good presentaion of enzyme mechanisms.
Campbell does a really good job in his figure 9 of 401lec15ball.pdf showing how a different fit is responsible for the different enzyme specificites of the serine proteases, (Trypsin, Chymotrypsin and Elastase).On pages 8 - 11 of 401lec15ball.pdf he goes on to discuss the mechanism of catalysis where the conformation and fit are of only incidental importance.

Thats it for the short answer, and we begin the lOng answer, driving more at what has replaced the Enzyme "Lock and Key" analogy, which is simply a great deal of detailed knowledge. Lets look at why practicing biochemists, molecular biologists and drug designers never think about "Lock and Key".

Enzymes are important because they catalyze biolgical pathways.
Almost all Enzymes are proteins, though some (the ribosome in protein synthesis is the significant example) also incorporate RNA.

A good source for information about well know pathways is KEGG:
http://www.genome.jp/kegg/pathway.html
My particular favorite pathway is oxidative phosporylation and ATP synthesis:
http://www.genome.jp/kegg/pathway/map/map00190.html

For many proteins we have good crystal structures ( or NM srtuctures).
Experimentally determined protein structures are stored at the PDB, the Protein Data Bank at:

http://www.rcsb.org/pdb/Welcome.do

David S. Goodsell has an excelent set of very readable articles in the Molecule of the Month:
http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/alphabetical_list.html

This months article on Cytochrome P450 is very good example of what scientists do talk about in the place of "lock and key"
http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/current_month.html

If you want to understand where the molecular structures come from the XRAY Crystallography course at http://www.doe-mbi.ucla.edu/~sawaya/m230d/ is really excellent they walk you through the entire experimental process with lots of real examples and details. Their Model Buidling pages really help you understand the detailed knowledge that has replaced the lock and key analogy in modern biology. http://www.doe-mbi.ucla.edu/~sawaya/m230d/Modelbuilding/modelbuilding.html

Nebosa Jojic has done some very nice recent work on how Epitopes bind to MHC. Again when we talk about binding energies this is really a measure of how good is the fit between a molecule and the enzyme. Nebosa's recent paper in Bioinformatics give one example of the kinds of models that are being developed to superceed "Lock and Key"
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16873476&query_hl=1&itool=pubmed_docsum
His paper is available in full text, open access at:
http://bioinformatics.oxfordjournals.org/cgi/reprint/22/14/e227

We should probably mention PubMed:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed
The national library of medicine provides a searchable list of abstracts for recent research articles related to medicine. Some but not all of the articles listed are available open acess.

Another example of the kind of work that is possible with the detailed knowledge of protein structure is the design of a new drug for treating high blood pressure: Aliskerin. This drug was designed by looking at the fit or binding to the active site of the enzyme Renin.
"Structure-based design of aliskiren, a novel orally effective renin inhibitor." J.M. WOod et.al.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12927775&query_hl=4&itool=pubmed_DocSum

Thats about it for the long answer.

I think you have asked a fascinating question. Your intution that "there must be something more there" than the lock and key analogy was really a very good guide, to how nature works and what is known and what we can learn about how biological systems work. I'd like to encourage your curiosity and keep learning.

Answer 2

Lock-and-key was still being taught last time I checked. It's a pretty good analogy for the fit -- but of course, the key doesn't turn in the lock to unlock it, LOL.

Answer 3

I like the idea of currency you can pay as and when you want and also know you can afford it. If we resort to credit / bank cards only some may spend more money than should. I know some of the major stores where I live have started to refuse cheques and will only take cash or cards so that change has started already. Some have never had a bank account and like to have their small amount of money in "real cash". But yes I dont think it will be long before we end up in a cash and paper less financial situation.

Answer 4

There are two actually. The lock and key idea. And the induced fit idea. Induced fit says that it rougjly fits and adjusts later. Lock and key say that they are made for eachother. Im not sure i really understand your question though

Answer 5

The lock and key analogy is still being taught.

Answer 6

Induced fit is an improvisation on Lock and key Hypothesis

Answer 7

I was taught the "lock and key" analogy...

Answer 8

that's the analogy we used in my bio class.