|
|
| Line 1: |
Line 1: |
| [[Image:1dfp.jpg|left|200px]] | | {{Seed}} |
| | [[Image:1dfp.png|left|200px]] |
|
| |
|
| <!-- | | <!-- |
| Line 9: |
Line 10: |
| {{STRUCTURE_1dfp| PDB=1dfp | SCENE= }} | | {{STRUCTURE_1dfp| PDB=1dfp | SCENE= }} |
|
| |
|
| '''FACTOR D INHIBITED BY DIISOPROPYL FLUOROPHOSPHATE'''
| | ===FACTOR D INHIBITED BY DIISOPROPYL FLUOROPHOSPHATE=== |
|
| |
|
|
| |
|
| ==Overview==
| | <!-- |
| Factor D (D) is a serine protease, crucial for the activation of the alternative complement pathway. Only a limited number of general serine protease inhibitors are known to inhibit D, most of which covalently bind to the serine hydroxyl of the catalytic triad. The structure of the first enzyme:inhibitor covalent adduct of D with diisopropyl fluorophosphate (DIP:D) to a resolution of 2.4 A is described. The inhibited enzyme is similar in overall structure to the native enzyme and to trypsin, yet exhibits notable differences in the active site. One region of the active site is conserved between D and trypsin with respect to amino-acid sequence and to conformation. Another reflects the amino-acid substitutions and conformational flexibility between these enzymes. The active-site histidine residue is observed in the gauche+ conformation, not the normal gauche- orientation seen in the classic catalytic triad arrangement required for enzymatic activity in serine proteases. Comparisons of the active sites between native D, the DIP:D adduct, and DIP-inhibited trypsin have provided fundamental insights currently being employed in the design of novel small-molecule pharmaceutical agents capable of modulating the alternative complement pathway.
| | The line below this paragraph, {{ABSTRACT_PUBMED_15299948}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15299948 is the PubMed ID number. |
| | --> |
| | {{ABSTRACT_PUBMED_15299948}} |
|
| |
|
| ==About this Structure== | | ==About this Structure== |
| Line 33: |
Line 37: |
| [[Category: Hydrolase]] | | [[Category: Hydrolase]] |
| [[Category: Serine protease]] | | [[Category: Serine protease]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:48:12 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 23:00:36 2008'' |