3qpw

<StructureSection load='3qpw' size='340' side='right' caption='[[3qpw]], [[Resolution|resolution]] 2.25&Aring;' scene=''>

<table><tr><td colspan='2'>[[3qpw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QPW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QPW FirstGlance]. <br>

</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ALF:TETRAFLUOROALUMINATE+ION'>ALF</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PEP:PHOSPHOENOLPYRUVATE'>PEP</scene><br>

<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3qpu|3qpu]], [[3qpv|3qpv]]</td></tr>

<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PFKFB3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>

<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3qpw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qpw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qpw RCSB], [http://www.ebi.ac.uk/pdbsum/3qpw PDBsum]</span></td></tr>

<table>

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== Publication Abstract from PubMed ==

The molecular basis of Fructose-2,6-bisphosphatase (F-2,6-P(2) ase) of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB) was investigated using the crystal structures of the human inducible form (PFKFB3) in a phospho-enzyme intermediate state (PFKFB3-P*F-6-P), in a transition state-analogous complex (PFKFB3*AlF4), and in a complex with pyrophosphate (PFKFB3*PP(i) ) at resolutions of 2.45A, 2.2A, and 2.3A, respectively. Trapping the PFKFB3-P*F-6-P intermediate was achieved by flash cooling the crystal during the reaction, and the PFKFB3*AlF4 and PFKFB3*PP(i) complexes were obtained by soaking. The PFKFB3*AlF(4) and PFKFB3*PP(i) complexes resulted in removing F-6-P from the catalytic pocket. With these structures, the structures of the Michaelis complex and the transition state were extrapolated. For both the PFKFB3-P formation and break down, the phosphoryl donor and the acceptor are located within approximately 5.1A, and the pivotal point 2-P is on the same line, suggesting an "in-line" transfer with a direct inversion of phosphate configuration. The geometry suggests that NE2 of His253 undergoes a nucleophilic attack to form a covalent N-P bond, breaking the 2O-P bond in the substrate. The resulting high reactivity of the leaving group, 2O of F-6-P, is neutralized by a proton donated by Glu322. Negative charges on the equatorial oxygens of the transient bipyramidal phosphorane formed during the transfer are stabilized by Arg252, His387, and Asn259. The C-terminal domain (residues 440-446) was rearranged in PFKFB3*PP(i) , implying that this domain plays a critical role in binding of substrate to and release of product from the F-2,6-P(2) ase catalytic pocket. These findings provide a new insight into the understanding of the phosphoryl transfer reaction. Proteins 2011. (c) 2011 Wiley-Liss, Inc.

 

 

[[Category: Cavalier, M C.]]

[[Category: Kim, S G.]]

[[Category: Lee, Y H.]]

[[Category: Neau, D.]]

[[Category: Hydrolase]]

[[Category: Transferase]]