1cgh
From Proteopedia
(New page: 200px<br /> <applet load="1cgh" size="450" color="white" frame="true" align="right" spinBox="true" caption="1cgh, resolution 1.8Å" /> '''HUMAN CATHEPSIN G'''...) |
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caption="1cgh, resolution 1.8Å" /> | caption="1cgh, resolution 1.8Å" /> | ||
'''HUMAN CATHEPSIN G'''<br /> | '''HUMAN CATHEPSIN G'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The crystal structure of human neutrophil cathepsin G, complexed with the | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1CGH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Cathepsin_G Cathepsin G], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.20 3.4.21.20] Full crystallographic information is available from [http:// | + | 1CGH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Cathepsin_G Cathepsin G], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.20 3.4.21.20] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CGH OCA]. |
==Reference== | ==Reference== | ||
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[[Category: specificity]] | [[Category: specificity]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:05:50 2008'' |
Revision as of 10:05, 21 February 2008
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HUMAN CATHEPSIN G
Overview
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.
About this Structure
1CGH is a Single protein structure of sequence from Homo sapiens. Active as Cathepsin G, with EC number 3.4.21.20 Full crystallographic information is available from OCA.
Reference
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., Hof P, Mayr I, Huber R, Korzus E, Potempa J, Travis J, Powers JC, Bode W, EMBO J. 1996 Oct 15;15(20):5481-91. PMID:8896442
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