Biology Reference
In-Depth Information
efficient enclosure of the haem in a protein environment that is essentially
based on four
a
-helices (hence the 2/2 helical fold acronym). A key feature
emerging from the crystal structures is the presence (at least in groups
I and II) of strategic and 2/2Hb-specific protein matrix tunnels or cavities,
with conserved topology, which are held to support diffusion of small
physiological ligands to/from the haem. The variety of distal site haem
cavities, and the properties of the lining amino acids, is substantial and
compatible with the display of different (pseudo)enzymatic activities. These
are often related to detoxifying mechanisms devised by a pathogen in
response to nitrogen and oxygen reactive species produced by the host.
Other roles have been considered, although these are mainly hypothetic
rather than proved
in vivo
. Notably, based on affinity of kinetic consider-
ations, in just one case an intracellular O
2
transport/delivery role has been
considered. The haem distal site in 2/2Hbs (as in Mb and Hb) is suited to
bind small ligands, likely diatomic gaseous molecules, such as O
2
, NO,
and CO. Thus, compared to a classical enzyme acting on larger substrates,
exploring 2/2Hb functions
in vivo
appears more complex, despite the
extensive knowledge available on haem biochemistry. A further complicat-
ing factor is related to the pathogenicity of some 2/2Hb carrying microor-
ganisms, or to the limited knowledge we have on their lifestyles and basic
microbiology. After more than 15 years in this field, it is felt that one of
the main open challanges is a thorough analysis and description of 2/2Hb
in vivo
functions.
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