From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:2hpp.jpg|left|200px]] | + | {{Seed}} |
| | + | [[Image:2hpp.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_2hpp| PDB=2hpp | SCENE= }} | | {{STRUCTURE_2hpp| PDB=2hpp | SCENE= }} |
| | | | |
| - | '''STRUCTURES OF THE NONCOVALENT COMPLEXES OF HUMAN AND BOVINE PROTHROMBIN FRAGMENT 2 WITH HUMAN PPACK-THROMBIN'''
| + | ===STRUCTURES OF THE NONCOVALENT COMPLEXES OF HUMAN AND BOVINE PROTHROMBIN FRAGMENT 2 WITH HUMAN PPACK-THROMBIN=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | Both human and bovine prothrombin fragment 2 (the second kringle) have been cocrystallized separately with human PPACK (D-Phe-Pro-Arg)-thrombin, and the structures of these noncovalent complexes have been determined and refined (R = 0.155 and 0.157, respectively) at 3.3-A resolution using X-ray crystallographic methods. The kringles interact with thrombin at a site that has previously been proposed to be the heparin binding region. The latter is a highly electropositive surface near the C-terminal helix of thrombin abundant in arginine and lysine residues. These form salt bridges with acidic side chains of kringle 2. Somewhat unexpectedly, the negative groups of the kringle correspond to an enlarged anionic center of the lysine binding site of lysine binding kringles such as plasminogens K1 and K4 and TPA K2. The anionic motif is DGDEE in prothrombin kringle 2. The corresponding cationic center of the lysine binding site region has an unfavorable Arg70Asp substitution, but Lys35 is conserved. However, the folding of fragment 2 is different from that of prothrombin kringle 1 and other kringles: the second outer loop possesses a distorted two-turn helix, and the hairpin beta-turn of the second inner loop pivots at Val64 and Asp70 by 60 degrees. Lys35 is located on a turn of the helix, which causes it to project into solvent space in the fragment 2-thrombin complex, thereby devastating any vestige of the cationic center of the lysine binding site. Since fragment 2 has not been reported to bind lysine, it most likely has a different inherent folding conformation for the second outer loop, as has also been observed to be the case with TPA K2 and the urokinase kringle. The movement of the Val64-Asp70 beta-turn is most likely a conformational change accompanying complexation, which reveals a new heretofore unsuspected flexibility in kringles. The fragment 2-thrombin complex is only the second cassette module-catalytic domain structure to be determined for a multidomain blood protein and only the third domain-domain interaction to be described among such proteins, the others being factor Xa without a Gla domain and Ca2+ prothrombin fragment 1 with a Gla domain and a kringle.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_8387813}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 8387813 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_8387813}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 25: |
Line 29: |
| | [[Category: Padmanabhan, K.]] | | [[Category: Padmanabhan, K.]] |
| | [[Category: Tulinsky, A.]] | | [[Category: Tulinsky, A.]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:33:26 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 17:21:56 2008'' |
Revision as of 14:22, 27 July 2008
Template:STRUCTURE 2hpp
STRUCTURES OF THE NONCOVALENT COMPLEXES OF HUMAN AND BOVINE PROTHROMBIN FRAGMENT 2 WITH HUMAN PPACK-THROMBIN
Template:ABSTRACT PUBMED 8387813
About this Structure
2HPP is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structures of the noncovalent complexes of human and bovine prothrombin fragment 2 with human PPACK-thrombin., Arni RK, Padmanabhan K, Padmanabhan KP, Wu TP, Tulinsky A, Biochemistry. 1993 May 11;32(18):4727-37. PMID:8387813
Page seeded by OCA on Sun Jul 27 17:21:56 2008
