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2.7.1.40, EC 2.7.2.3, EC 4.1.2.13, EC 4.2.1.11, EC 5.3.1.1, EC 5.3.1.9, EC
5.4.2.1) thus, each of these enzymes allows for a peculiar sequence space to be
constructed and compared with the metabolic network space.
It is well known that the correlation of two protein distance spaces is a marker
of some form of interaction between the two molecules, and this feature is
routinely adopted for inferring protein-protein interactions. The need to support a
viable interaction between the two proteins imposes a mutual constraint
(resulting into a covariation) to the random mutation drift of the two systems.
This covariation results into correlated dissimilarity matrices (trees) relative
to the two proteins as for a suitable set of organisms. This is exactly what
we observed for the 11 common glycolysis/gluconeogenesis sequence based
dissimilarity matrices that were significantly correlated to each other. The same
was true when we correlated between the organisms dissimilarity matrix based
on metabolic networks with the single enzymes sequence spaces. The metabolic
network space scored the maximal correlation with the E.C. 4.2.1.11
(phosphopyruvate hydratase) sequence space correspondent to a Pearson r = 0.94,
p < 0.001.
This implies an almost perfect coincidence of the two spaces.
Phosphopyruvate hydratase is the enzyme at the interface between the glycolysis
and gluconeogenesis modules. Moreover, it represents the link of the module
with other biochemical processes like photosynthesis, aminoacid biosynthesis
and cytrate cycle. This 'frontier' position is registered by the loading of its
dissimilarity space on components other than the common variation axis.
On the basis of such considerations, we may hypothesize that it represents a
crucial point of the module and a sort of 'summary' of the entire network
behavior. This is probably the reason of the almost perfect linear superposition
between metabolic and sequence spaces.
It is worth considering the genesis of the resemblance between metabolic-
wiring and phosphopyruvate hydratase sequence based classifications. In the
metabolic-wiring space the difference between two organisms A and B is based
on the fact a given reaction can take place into organism A but not in the
organism B or viceversa. This in general comes from the fact a specific enzyme
able to catalyse that reaction is present only in one of the two organisms.
The great majority of the enzymes making the between organisms differences
has to do with the processing of the 'reactant subset'. This is in line with the
presence of specific 'ecological niches' for the analysed microrganims that allow
certain species to grow in a given environment by the utilization of a specific
carbon source.
