| Literature References | 1. DICKERSON, R.E. AND GEIS, I.
Hemoglobin: Structure, Function, Evolution and Pathology.
THE BENJAMIN/CUMMINGS PUBLISHING COMPANY, 1983.
2. KAPP, O.H., MOENS, L., VANFLETEREN, J., TROTMAN, C.N.A., SUZUKI, T.
AND VINOGRADOV, S.N.
Alignment of 700 globin sequences: Extent of amino acid substitution
and its correlation with variation in volume.
PROTEIN SCI. 4 2179-2190 (1995).
3. MOENS, L., VANFLETEREN, J., VAN DE PEER, Y., PEETERS, K., KAPP, O.,
CZELUZNIAK, J., GOODMAN, M., BLAXTER, M. AND VINOGRADOV, S.
Globins in nonvertebrate species: dispersal by horizontal gene transfer
and evolution of the structure-function relationships.
MOL.BIOL.EVOL. 13 324-333 (1996).
4. WHITAKER, T.L., BERRY, M.B., HO, E.L., HARGROVE, M.S., PHILLIPS, G.N.,
KOMIYAMA, N.H., NAGAI, K. AND OLSON, J.S.
The D-helix in myoglobin and in the beta subunit of hemoglobin is required
for the retention of heme.
BIOCHEMISTRY 34 8221-8226 (1995).
5. CHAPMAN, B.S., TOBIN A.J., HOOD L.E.
Complete amino acid sequence of the major early embryonic alpha-like
globins of the chicken.
J.BIOL.CHEM. 255 9051-9059 (1980).
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| Documentation | Globins are haem-containing proteins involved in dioxygen binding and/or
transport [1]. At present, more than 700 globin sequences are known [2].
It has been proposed that all globins have evolved from a family of
ancestral, approximately 17kDa haemoproteins that displayed the globin
fold and functioned as redox proteins [3]. The globin superfamily includes
vertebrate haemoglobins (Hb); vertebrate myoglobins (Mb); invertebrate
globins; plant leghaemoglobins; and bacterial flavohaemoglobins.
The function of haemoglobins (Hb) is transport of dioxygen in blood plasma.
Hb binds O(2) in the reduced [Fe(II)] state. The Hb molecule exists as a
tetramer, typically of two alpha- and two beta-globin chains, which form
a well-defined quaternary structure. Each monomer binds iron protoporphyrin
IX (haem).
The 3D structures of a great number of vertebrate Hbs in various states
are known. The protein is largely alpha-helical, eight conserved helices
(A to H) providing the scaffold for a well-defined haem-binding pocket
(Hb alpha subunits lack helix D [4]). The imidazole ring of the "proximal"
His residue provides the fifth haem iron ligand; the other axial haem iron
position remains essentially free for O(2) coordination. Conserved "distal"
His and Val residues block an unhindered access to the sixth coordination
site so that a controlled binding of small molecules may result only as a
consequence of side-chain dynamics of the protein [1]. O(2) binding results
in a transition from high-spin to low-spin iron, with accompanying changes
in the Fe-N bond lengths and coordination geometry. In Hb, these subtle
changes lead to the well-known cooperative effect. At the quaternary
structure level, O(2) binding induces relative reorientation of the
[alpha-1, beta-1] and [alpha-2, beta-2] dimers.
It has been hypothesised that the embryonic alpha-haemoglobin family
diverged considerably earlier than the beta-haemoglobin line [5]. This
is reflected in a greater variability amongst alpha sequences, such that
two distinct sub-groups may be distinguished; these have been designated
zeta and pi.
PIHAEM is a 4-element fingerprint that provides a signature for the
pi family of haemoglobins. The fingerprint was derived from an initial
alignment of 3 sequences: the motifs were drawn from conserved regions
spanning the full alignment length, focusing on those regions that
characterise the pi haemoglobins but distinguish them from the rest of
the globin family - motif 1 encompasses the majority of helix 1, helix 2
and the N-terminal section of helix 3; motif 2 spans the C-terminal half
of the loop between helices 4 and 5, leading into helix 5; motif 3 spans
helices 6, 7 and the N-terminus of helix 8; and motif 4 spans the C-terminal
half of helix 9 and part of the following loop region. A single iteration
on OWL30.0 was required to reach convergence, no further sequences being
identified beyond the starting set. Several partial matches were also found,
all of which are alpha-like haemoglobins.
An update on SPTR37_9f identified a true set of 2 sequences, and 7
partial matches.
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