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PDBsum entry 1cgh
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Hydrolase/hydrolase inhibitor
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PDB id
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1cgh
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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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The 1.8 a crystal structure of human cathepsin g in complex with suc-Val-Pro-Phep-(Oph)2: a janus-Faced proteinase with two opposite specificities.
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Authors
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P.Hof,
I.Mayr,
R.Huber,
E.Korzus,
J.Potempa,
J.Travis,
J.C.Powers,
W.Bode.
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Ref.
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Embo J, 1996,
15,
5481-5491.
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PubMed id
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Abstract
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The crystal structure of human neutrophil cathepsin G, complexed with the
peptidyl phosphonate inhibitor Suc-Val-Pro-PheP-(OPh)2, has been determined to a
resolution of 1.8 A using Patterson search techniques. The cathepsin G structure
shows the polypeptide fold characteristic of trypsin-like serine proteinases and
is especially similar to rat mast cell proteinase II. Unique to cathepsin G,
however, is the presence of Glu226 (chymotrypsinogen numbering), which is
situated at the bottom of the S1 specificity pocket, dividing it into two
compartments. For this reason, the benzyl side chain of the inhibitor PheP
residue does not fully occupy the pocket but is, instead, located at its
entrance. Its positively charged equatorial edge is involved in a favourable
electrostatic interaction with the negatively charged carboxylate group of
Glu226. Arrangement of this Glu226 carboxylate would also allow accommodation of
a Lys side chain in this S1 pocket, in agreement with the recently observed
cathepsin G preference for Lys and Phe at P1. The cathepsin G complex with the
covalently bound phosphonate inhibitor mimics a tetrahedral substrate
intermediate. A comparison of the Arg surface distributions of cathepsin G,
leukocyte elastase and rat mast cell protease II shows no simple common
recognition pattern for a mannose-6-phosphate receptor-independent targeting
mechanism for sorting of these granular proteinases.
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