We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

1taw

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1taw.gif|left|200px]]
+
{{Seed}}
 +
[[Image:1taw.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1taw| PDB=1taw | SCENE= }}
{{STRUCTURE_1taw| PDB=1taw | SCENE= }}
-
'''BOVINE TRYPSIN COMPLEXED TO APPI'''
+
===BOVINE TRYPSIN COMPLEXED TO APPI===
-
==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.
+
The line below this paragraph, {{ABSTRACT_PUBMED_9300481}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 9300481 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_9300481}}
==About this Structure==
==About this Structure==
Line 30: Line 34:
[[Category: Protease-substrate interaction]]
[[Category: Protease-substrate interaction]]
[[Category: Serine protease]]
[[Category: Serine protease]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 09:45:05 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 07:22:44 2008''

Revision as of 04:22, 29 July 2008

Image:1taw.png


PDB ID 1taw

Drag the structure with the mouse to rotate
1taw, resolution 1.80Å ()
Ligands:
Gene: A4 (Homo sapiens)
Activity: Trypsin, with EC number 3.4.21.4
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml



BOVINE TRYPSIN COMPLEXED TO APPI

Template:ABSTRACT PUBMED 9300481

About this Structure

1TAW 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

Page seeded by OCA on Tue Jul 29 07:22:44 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1taw"
Personal tools