1ca0
From Proteopedia
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| - | [[Image:1ca0.gif|left|200px]] | + | [[Image:1ca0.gif|left|200px]] |
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| - | '''BOVINE CHYMOTRYPSIN COMPLEXED TO APPI''' | + | {{Structure |
| + | |PDB= 1ca0 |SIZE=350|CAPTION= <scene name='initialview01'>1ca0</scene>, resolution 2.1Å | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Chymotrypsin Chymotrypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.1 3.4.21.1] | ||
| + | |GENE= A4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus]), A4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''BOVINE CHYMOTRYPSIN COMPLEXED TO APPI''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1CA0 is a [ | + | 1CA0 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CA0 OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal structures of bovine chymotrypsin and trypsin complexed to the inhibitor domain of Alzheimer's amyloid beta-protein precursor (APPI) and basic pancreatic trypsin inhibitor (BPTI): engineering of inhibitors with altered specificities., Scheidig AJ, Hynes TR, Pelletier LA, Wells JA, Kossiakoff AA, Protein Sci. 1997 Sep;6(9):1806-24. PMID:[http:// | + | Crystal structures of bovine chymotrypsin and trypsin complexed to the inhibitor domain of Alzheimer's amyloid beta-protein precursor (APPI) and basic pancreatic trypsin inhibitor (BPTI): engineering of inhibitors with altered specificities., Scheidig AJ, Hynes TR, Pelletier LA, Wells JA, Kossiakoff AA, Protein Sci. 1997 Sep;6(9):1806-24. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9300481 9300481] |
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: Chymotrypsin]] | [[Category: Chymotrypsin]] | ||
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[[Category: complex (serine protease/inhibitor)]] | [[Category: complex (serine protease/inhibitor)]] | ||
[[Category: inhibitor]] | [[Category: inhibitor]] | ||
| - | [[Category: protease-substrate | + | [[Category: protease-substrate interaction]] |
[[Category: serine protease]] | [[Category: serine protease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:21:48 2008'' |
Revision as of 08:21, 20 March 2008
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| , resolution 2.1Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | A4 (Bos taurus), A4 (Homo sapiens) | ||||||
| Activity: | Chymotrypsin, with EC number 3.4.21.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
BOVINE CHYMOTRYPSIN COMPLEXED TO APPI
Contents |
Overview
The crystal structures of the inhibitor domain of Alzheimer's amyloid beta-protein precursor (APPI) complexed to bovine chymotrypsin (C-APPI) and trypsin (T-APPI) and basic pancreatic trypsin inhibitor (BPTI) bound to chymotrypsin (C-BPTI) have been solved and analyzed at 2.1 A, 1.8 A, and 2.6 A resolution, respectively. APPI and BPTI belong to the Kunitz family of inhibitors, which is characterized by a distinctive tertiary fold with three conserved disulfide bonds. At the specificity-determining site of these inhibitors (P1), residue 15(I)4 is an arginine in APPI and a lysine in BPTI, residue types that are counter to the chymotryptic hydrophobic specificity. In the chymotrypsin complexes, the Arg and Lys P1 side chains of the inhibitors adopt conformations that bend away from the bottom of the binding pocket to interact productively with elements of the binding pocket other than those observed for specificity-matched P1 side chains. The stereochemistry of the nucleophilic hydroxyl of Ser 195 in chymotrypsin relative to the scissile P1 bond of the inhibitors is identical to that observed for these groups in the trypsin-APPI complex, where Arg 15(I) is an optimal side chain for tryptic specificity. To further evaluate the diversity of sequences that can be accommodated by one of these inhibitors, APPI, we used phage display to randomly mutate residues 11, 13, 15, 17, and 19, which are major binding determinants. Inhibitors variants were selected that bound to either trypsin or chymotrypsin. As expected, trypsin specificity was principally directed by having a basic side chain at P1 (position 15); however, the P1 residues that were selected for chymotrypsin binding were His and Asn, rather than the expected large hydrophobic types. This can be rationalized by modeling these hydrophilic side chains to have similar H-bonding interactions to those observed in the structures of the described complexes. The specificity, or lack thereof, for the other individual subsites is discussed in the context of the "allowed" residues determined from a phage display mutagenesis selection experiment.
Disease
Known diseases associated with this structure: Alzheimer disease-1, APP-related OMIM:[104760], Amyloidosis, cerebroarterial, Dutch type OMIM:[104760], Amyloidosis, cerebroarterial, Iowa type OMIM:[104760], Blood group, P system OMIM:[607922]
About this Structure
1CA0 is a Protein complex structure of sequences from Bos taurus and Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structures of bovine chymotrypsin and trypsin complexed to the inhibitor domain of Alzheimer's amyloid beta-protein precursor (APPI) and basic pancreatic trypsin inhibitor (BPTI): engineering of inhibitors with altered specificities., Scheidig AJ, Hynes TR, Pelletier LA, Wells JA, Kossiakoff AA, Protein Sci. 1997 Sep;6(9):1806-24. PMID:9300481
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