|
|
| Line 1: |
Line 1: |
| [[Image:2i1v.jpg|left|200px]] | | {{Seed}} |
| | [[Image:2i1v.png|left|200px]] |
|
| |
|
| <!-- | | <!-- |
| Line 9: |
Line 10: |
| {{STRUCTURE_2i1v| PDB=2i1v | SCENE= }} | | {{STRUCTURE_2i1v| PDB=2i1v | SCENE= }} |
|
| |
|
| '''Crystal structure of PFKFB3 in complex with ADP and Fructose-2,6-bisphosphate'''
| | ===Crystal structure of PFKFB3 in complex with ADP and Fructose-2,6-bisphosphate=== |
|
| |
|
|
| |
|
| ==Overview==
| | <!-- |
| To understand the molecular basis of a phosphoryl transfer reaction catalyzed by the 6-phosphofructo-2-kinase domain of the hypoxia-inducible bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3), the crystal structures of PFKFB3AMPPCPfructose-6-phosphate and PFKFB3ADPphosphoenolpyruvate complexes were determined to 2.7 A and 2.25 A resolution, respectively. Kinetic studies on the wild-type and site-directed mutant proteins were carried out to confirm the structural observations. The experimentally varied liganding states in the active pocket cause no significant conformational changes. In the pseudo-substrate complex, a strong direct interaction between AMPPCP and fructose-6-phosphate (Fru-6-P) is found. By virtue of this direct substrate-substrate interaction, Fru-6-P is aligned with AMPPCP in an orientation and proximity most suitable for a direct transfer of the gamma-phosphate moiety to 2-OH of Fru-6-P. The three key atoms involved in the phosphoryl transfer, the beta,gamma-phosphate bridge oxygen atom, the gamma-phosphorus atom, and the 2-OH group are positioned in a single line, suggesting a direct phosphoryl transfer without formation of a phosphoenzyme intermediate. In addition, the distance between 2-OH and gamma-phosphorus allows the gamma-phosphate oxygen atoms to serve as a general base catalyst to induce an "associative" phosphoryl transfer mechanism. The site-directed mutant study and inhibition kinetics suggest that this reaction will be catalyzed most efficiently by the protein when the substrates bind to the active pocket in an ordered manner in which ATP binds first.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17499765}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17499765 is the PubMed ID number. |
| | --> |
| | {{ABSTRACT_PUBMED_17499765}} |
|
| |
|
| ==About this Structure== | | ==About this Structure== |
| Line 31: |
Line 35: |
| [[Category: Ternary product complex]] | | [[Category: Ternary product complex]] |
| [[Category: Transferase]] | | [[Category: Transferase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 7 08:44:20 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 08:19:37 2008'' |
