On 17 Apr 1997 at 09:08 Yang-Seok Kim wrote
> Vitamin B1 synthetic genes are scattered in E.coli chromosome. However, I
> found, two of them are joined and bacame bifunctional protein in plant.
> Does anybody know the benifit of bifuntionallity in evolution or the
> reference papers about bifuntionallity?"
Bifunctional (or even multifunctional) proteins are ubiquitous in Nature.
Some time ago I became interested in this subject and started collecting
papers on multifunctional proteins (I was looking for examples where there
was also channelling between the different active sites in the
polypeptide). There are quite a large number of multifunctional enzymes,
many more than I was expecting, and they are widespread through bacteria,
yeasts, plants, animals, etc.
On 25 Apr 97 at 1:39, Athel wrote:
> If the two enzymes catalyse non-consecutive reactions it isn't easy to
> think of advantages, but if they are consecutive then in principle having
> a bifunctional protein allows direct transfer of the common intermediate
> from one active site to another (i.e. channelling).
I will make no comments on their "advantage" as that dependends on the
environment in which the organisms in question live. But I can make some
comments on the properties that bifunctional enzymes have different to the
equivalent pair of independent enzymes:
1- as pointed by Athel one can think that fusion of the two enzymes
facilitates some form of channelling of their common intermediate (if they
are consecutive enzymes). This does not have to ocurr through an actual
physical channel (like in the Tryptophan synthase of E.coli and
S.typhimurium), in fact there is one example of a bifunctional enzyme
that apparently channels the intermediate between the two active sites
through electrostatic interactions on its surface (the enzyme is
dihydrofolate reductase:thymidylate synthase from Leishmania major see
Knighton et al. (1994) Nature Struct.Biol. 1, 186-194). Another example
of a bifunctional enzyme where channelling seems to take place is E.coli's
phosphoribosylanthranilate isomerase:indoleglycerolphosphate synthase
(Wilmans et al. (1992) J.Mol.Bio. 223, 477-507).
2- even if the two enzymes don't catalyse consecutive steps in metabolism,
their expression cannot be controled independently and their concentration
will always be equimolar. This in itself is a form of "enzyme-enzyme"
interaction (I have never seen this discussed in the literature, if anyone
has I'd like a reference). This is something I have studied in my PhD but
have so far not yet got around publishing. The paper by Cascante et al.
(1990) Eur.J.Biochem. 192, 369-371 might also be relevant on this.
3- in the bifunctional enzyme one can imagine situations in which
ligand binding on one activite site has effects on the conformation of
the polypeptide affecting the activity of the other active site. In
addition, the fusion might have provided one active site to respond
allosterically to a third ligand that was only an allosteric modulator of
the other active site. Again this will result in some form of
4- a bifunctional enzyme costs less to express than the corresponding pair
of independent enzymes. However I don't think this is that important as
the difference must be small.
I'm sure one can think of other properties that are novel to the
bifunctional enzyme (in relation with the independent pair).
On 25 Apr 97 at 1:39, Athel also wrote:
> In the published literature you would find it useful to look up papers
> and reviews by (among others) Paul Srere or Judit Ovadi... Judit has a
> recent book (sorry, I can't find it at this moment so I can't quote the
> title) published by R. G. Landes (1995).
Ovadi, J. (1995) "Cell architecture and metabolic channeling" R.G Landes
Company, Austin, Texas.
Welch, G.R. (Ed.) (1985) Organized multienzyme systems. Catalytic
properties. Academic Press, New york.
Welch, G.R. and Clegg, J.S. (Eds.) (1987) Organization of cell metabolism.
Plenum Press, New York.
see also the following web pages for more references on this subject:
Pedro Mendes Inst. Biological Sciences
prm at aber.ac.uk (home: pedro at enzyme.demon.co.uk) Univ. Wales, Aberystwyth,
http://gepasi.dbs.aber.ac.uk/pedro/prmhome.htm Ceredigion SY23 3DA, U.K.
http://gepasi.dbs.aber.ac.uk/softw/gepasi.html FAX: +44 (0)1970 622350