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PDBsum entry 1qmu
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Carboxypeptidase
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PDB id
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1qmu
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of avian carboxypeptidase d domain ii: a prototype for the regulatory metallocarboxypeptidase subfamily.
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Authors
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F.X.Gomis-Rüth,
V.Companys,
Y.Qian,
L.D.Fricker,
J.Vendrell,
F.X.Avilés,
M.Coll.
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Ref.
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EMBO J, 1999,
18,
5817-5826.
[DOI no: ]
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PubMed id
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Abstract
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The crystal structure of domain II of duck carboxypeptidase D, a
prohormone/propeptide processing enzyme integrated in a three repeat tandem in
the natural system, has been solved, constituting a prototype for members of the
regulatory metallocarboxypeptidase subfamily. It displays a 300 residue
N-terminal alpha/beta-hydrolase subdomain with overall topological similarity to
and general coincidence of the key catalytic residues with the archetypal
pancreatic carboxypeptidase A. However, numerous significant
insertions/deletions in segments forming the funnel-like access to the active
site explain differences in specificity towards larger protein substrates or
inhibitors. This alpha/beta-hydrolase subdomain is followed by a C-terminal 80
residue beta-sandwich subdomain, unique for these regulatory metalloenzymes and
topologically related to transthyretin and sugar-binding proteins. The structure
described here establishes the fundamentals for a better understanding of the
mechanism ruling events such as prohormone processing and will enable modelling
of regulatory carboxypeptidases as well as a more rational design of inhibitors
of carboxypeptidase D.
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Figure 2.
Figure 2 (A) Stereo ribbon cartoon of CPD-2. The termini are
labelled, as are the helices (A -I) and strands (I -XV). The
zinc ion, the zinc-coordinating protein side chains, the
N-linked glycosylation sites, the disulfide bond and the sulfate
anions are also displayed. (B) Topology scheme of the CPD-2
polypeptide fold, with  -helices
indicated by cylinders and  -strands
by arrows.
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Figure 4.
Figure 4 (A) Stereo view of the overlaid C[  ]-carbon
structures of CPD-2 (CP subdomain only; yellow sticks), CPA
(green sticks) and CPT (magenta sticks). The zinc ion (violet
sphere) belongs to the CPD-2 structure. Selected CPD-2 residues
are labelled. (B) View facing the funnel surrounding the active
site cleft superimposed with its solid Connolly surface
displaying the electrostatic potential [ranging from -15 k[B]T/e
(red) to +15 k[B]T/e (blue)] of CPD-2 (left), CPA (centre) and
CPT (right). The modelled substrate (CPD-2) and the coordinates
(PDB access code 6cpa) of a phosphonate inhibitor (CPA and CPT)
are also displayed, respectively, to highlight the active site.
(C) Stereo view of the C[ ]-carbon
structures of CPD-2 (CP subdomain only; yellow sticks) and CPA
(green sticks) in its complex with potato carboxypeptidase
inhibitor (blue sticks) (PDB access code 4cpa). Steric hindrance
prevents the latter from binding the regulatory CP. The zinc ion
(violet sphere) belongs to the CPD-2 structure. Some CPD-2
residues are labelled.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(1999,
18,
5817-5826)
copyright 1999.
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