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PDBsum entry 1l2e
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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 and biochemical characterization of human kallikrein 6 reveals that a trypsin-Like kallikrein is expressed in the central nervous system.
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Authors
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M.J.Bernett,
S.I.Blaber,
I.A.Scarisbrick,
P.Dhanarajan,
S.M.Thompson,
M.Blaber.
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Ref.
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J Biol Chem, 2002,
277,
24562-24570.
[DOI no: ]
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PubMed id
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Abstract
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The human kallikreins are a large multigene family of closely related
serine-type proteases. In this regard, they are similar to the multigene
kallikrein families characterized in mice and rats. There is a much more
extensive body of knowledge regarding the function of mouse and rat kallikreins
in comparison with the human kallikreins. Human kallikrein 6 has been proposed
as the homologue to rat myelencephalon-specific protease, an arginine-specific
degradative-type protease abundantly expressed in the central nervous system and
implicated in demyelinating disease. We present the x-ray crystal structure of
mature, active recombinant human kallikrein 6 at 1.75-A resolution. This high
resolution model provides the first three-dimensional view of one of the human
kallikreins and one of only a few structures of serine proteases predominantly
expressed in the central nervous system. Enzymatic data are presented that
support the identification of human kallikrein 6 as the functional homologue of
rat myelencephalon-specific protease and are corroborated by a molecular
phylogenetic analysis. Furthermore, the x-ray data provide support for the
characterization of human kallikrein 6 as a degradative protease with structural
features more similar to trypsin than the regulatory kallikreins.
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Figure 5.
Fig. 5. Relaxed stereo ribbon diagrams of hK6 (top
panel), bovine trypsin (1CE5; middle panel), and mouse glandular
kallikrein 13 (mK13) (1AO5; lower panel). Orientation is
intended to show the active site cleft with locations of
catalytic triad (His57, Asp102, and Ser195), S1 site (Asp192),
and bound benzamidine inhibitor (if present). Also indicated are
the locations of the autolysis sites in hK6 and bovine trypsin.
The two canonical autolysis sites in the mouse kallikreins are
indicated using the structure of mK13. Also shown are the
locations of the loop regions 92-102 (blue), 141-152 (magenta),
and 172-178 (green) that border the active site.
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Figure 7.
Fig. 7. Relaxed stereo diagram showing details of the S1
binding pocket in hK6 (upper panel), bovine trypsin (1CE5;
middle panel), and porcine kallikrein (2PKA, lower panel). The
hydrogen bonding interactions of the bound benzamidine inhibitor
are shown using broken lines (residue positions 191-193 are
omitted for clarity).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2002,
277,
24562-24570)
copyright 2002.
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