From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:1r9n.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1r9n.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_1r9n| PDB=1r9n | SCENE= }} | | {{STRUCTURE_1r9n| PDB=1r9n | SCENE= }} |
| | | | |
| - | '''Crystal Structure of human dipeptidyl peptidase IV in complex with a decapeptide (tNPY) at 2.3 Ang. Resolution'''
| + | ===Crystal Structure of human dipeptidyl peptidase IV in complex with a decapeptide (tNPY) at 2.3 Ang. Resolution=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | Dipeptidyl peptidase IV (DPPIV) is a member of the prolyl oligopeptidase family of serine proteases. DPPIV removes dipeptides from the N terminus of substrates, including many chemokines, neuropeptides, and peptide hormones. Specific inhibition of DPPIV is being investigated in human trials for the treatment of type II diabetes. To understand better the molecular determinants that underlie enzyme catalysis and substrate specificity, we report the crystal structures of DPPIV in the free form and in complex with the first 10 residues of the physiological substrate, Neuropeptide Y (residues 1-10; tNPY). The crystal structure of the free form of the enzyme reveals two potential channels through which substrates could access the active site-a so-called propeller opening, and side opening. The crystal structure of the DPPIV/tNPY complex suggests that bioactive peptides utilize the side opening unique to DPPIV to access the active site. Other structural features in the active site such as the presence of a Glu motif, a well-defined hydrophobic S1 subsite, and minimal long-range interactions explain the substrate recognition and binding properties of DPPIV. Moreover, in the DPPIV/tNPY complex structure, the peptide is not cleaved but trapped in a tetrahedral intermediate that occurs during catalysis. Conformational changes of S630 and H740 between DPPIV in its free form and in complex with tNPY were observed and contribute to the stabilization of the tetrahedral intermediate. Our results facilitate the design of potent, selective small molecule inhibitors of DPPIV that may yield compounds for the development of novel drugs to treat type II diabetes.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_14718659}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 14718659 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_14718659}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 35: |
Line 39: |
| | [[Category: Eight-bladed beta propeller]] | | [[Category: Eight-bladed beta propeller]] |
| | [[Category: Serine protease]] | | [[Category: Serine protease]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:14:45 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 17:44:39 2008'' |
Revision as of 14:44, 28 July 2008
Template:STRUCTURE 1r9n
Crystal Structure of human dipeptidyl peptidase IV in complex with a decapeptide (tNPY) at 2.3 Ang. Resolution
Template:ABSTRACT PUBMED 14718659
About this Structure
1R9N is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of human dipeptidyl peptidase IV in complex with a decapeptide reveals details on substrate specificity and tetrahedral intermediate formation., Aertgeerts K, Ye S, Tennant MG, Kraus ML, Rogers J, Sang BC, Skene RJ, Webb DR, Prasad GS, Protein Sci. 2004 Feb;13(2):412-21. Epub 2004 Jan 10. PMID:14718659
Page seeded by OCA on Mon Jul 28 17:44:39 2008
