 |
PDBsum entry 1xfb
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Structure of human brain fructose 1,6-(Bis)phosphate aldolase: linking isozyme structure with function.
|
|
|
Authors
|
|
T.L.Arakaki,
J.A.Pezza,
M.A.Cronin,
C.E.Hopkins,
D.B.Zimmer,
D.R.Tolan,
K.N.Allen.
|
|
|
Ref.
|
|
Protein Sci, 2004,
13,
3077-3084.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Fructose-1,6-(bis)phosphate aldolase is a ubiquitous enzyme that catalyzes the
reversible aldol cleavage of fructose-1,6-(bis)phosphate and fructose
1-phosphate to dihydroxyacetone phosphate and either glyceral-dehyde-3-phosphate
or glyceraldehyde, respectively. Vertebrate aldolases exist as three isozymes
with different tissue distributions and kinetics: aldolase A (muscle and red
blood cell), aldolase B (liver, kidney, and small intestine), and aldolase C
(brain and neuronal tissue). The structures of human aldolases A and B are known
and herein we report the first structure of the human aldolase C, solved by
X-ray crystallography at 3.0 A resolution. Structural differences between the
isozymes were expected to account for isozyme-specific activity. However, the
structures of isozymes A, B, and C are the same in their overall fold and active
site structure. The subtle changes observed in active site residues Arg42,
Lys146, and Arg303 are insufficient to completely account for the
tissue-specific isozymic differences. Consequently, the structural analysis has
been extended to the isozyme-specific residues (ISRs), those residues conserved
among paralogs. A complete analysis of the ISRs in the context of this structure
demonstrates that in several cases an amino acid residue that is conserved among
aldolase C orthologs prevents an interaction that occurs in paralogs. In
addition, the structure confirms the clustering of ISRs into discrete patches on
the surface and reveals the existence in aldolase C of a patch of
electronegative residues localized near the C terminus. Together, these
structural changes highlight the differences required for the tissue and kinetic
specificity among aldolase isozymes.
|
|
|
|
|
|
|
|
Figure 2.
Figure 2. The active site of aldolase C (red) with residues
depicted as ball-and-stick, overlaid with the active site
residues of aldolase A (blue; PDB accession code 1ALD [PDB]
) and aldolase B (green; PDB accession code 1QO5 [PDB]
).
|
|
Figure 3.
Figure 3. Stereo view of the active site residues of the
aldolase C structure. The residues are shown as ball-and-stick
models. The 2Fo-Fc electron density map contoured at 1  is depicted
as blue cages.
|
|
|
|
|
|
The above figures are
reprinted
by permission from the Protein Society:
Protein Sci
(2004,
13,
3077-3084)
copyright 2004.
|
|
|
|
|
|
|
