4he2: Difference between revisions
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==Crystal structure of human muscle fructose-1,6-bisphosphatase Q32R mutant complex with AMP== | |||
<StructureSection load='4he2' size='340' side='right' caption='[[4he2]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4he2]] 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=4HE2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HE2 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO3:PHOSPHITE+ION'>PO3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4he0|4he0]], [[4he1|4he1]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fbp2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Fructose-bisphosphatase Fructose-bisphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.11 3.1.3.11] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4he2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4he2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4he2 RCSB], [http://www.ebi.ac.uk/pdbsum/4he2 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Fructose-1,6-bisphosphatase, a key enzyme in gluconeogenesis, is subject to metabolic regulation. The human muscle isozyme is significantly more sensitive towards the allosteric inhibitor, AMP, than the liver isoform. Here we report crystal structures and kinetic studies for wild-type human muscle Fru-1,6-Pase, the AMP-bound (1.6 A), and product-bound complexes of the Q32R mutant, which was firstly introduced by an error in the cloning. Our high-resolution structure reveals for the first time that the higher sensitivity of the muscle isozyme towards AMP originates from an additional water-mediated, H-bonded network established between AMP and the binding pocket. Also present in our structures are a metaphosphate molecule, alternate conformations of Glu97 coordinating Mg2+, and possible metal migration during catalysis. Although the individual subunit is similar to previously reported Fru-1,6-Pase structures, the tetrameric assembly of all these structures deviates from the canonical R- or T-states, representing novel tetrameric assemblies. Intriguingly, the concentration of AMP required for 50% inhibition of the Q32R mutant is increased 19-fold, and the cooperativity of both AMP and Mg2+ is abolished or decreased. These structures demonstrate the Q32R mutation affects the conformations of both N-terminal residues and the dynamic loop 52-72. Also importantly, structural comparison indicates that this mutation in helix alpha2 is detrimental to the R-to-T conversion as evidenced by the absence of quaternary structural changes upon AMP binding, providing direct evidence for the critical role of helix alpha2 in the allosteric signal transduction. | |||
Crystal Structures of Human Muscle Fructose-1,6-Bisphosphatase: Novel Quaternary States, Enhanced AMP Affinity, and Allosteric Signal Transmission Pathway.,Shi R, Chen ZY, Zhu DW, Li C, Shan Y, Xu G, Lin SX PLoS One. 2013 Sep 27;8(9):e71242. PMID:24086250<ref>PMID:24086250</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Fructose-bisphosphatase]] | [[Category: Fructose-bisphosphatase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Lin, S X | [[Category: Lin, S X]] | ||
[[Category: Shi, R | [[Category: Shi, R]] | ||
[[Category: Zhu, D W | [[Category: Zhu, D W]] | ||
[[Category: Allosteric enzyme]] | [[Category: Allosteric enzyme]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
Revision as of 16:11, 21 December 2014
Crystal structure of human muscle fructose-1,6-bisphosphatase Q32R mutant complex with AMPCrystal structure of human muscle fructose-1,6-bisphosphatase Q32R mutant complex with AMP
Structural highlights
Publication Abstract from PubMedFructose-1,6-bisphosphatase, a key enzyme in gluconeogenesis, is subject to metabolic regulation. The human muscle isozyme is significantly more sensitive towards the allosteric inhibitor, AMP, than the liver isoform. Here we report crystal structures and kinetic studies for wild-type human muscle Fru-1,6-Pase, the AMP-bound (1.6 A), and product-bound complexes of the Q32R mutant, which was firstly introduced by an error in the cloning. Our high-resolution structure reveals for the first time that the higher sensitivity of the muscle isozyme towards AMP originates from an additional water-mediated, H-bonded network established between AMP and the binding pocket. Also present in our structures are a metaphosphate molecule, alternate conformations of Glu97 coordinating Mg2+, and possible metal migration during catalysis. Although the individual subunit is similar to previously reported Fru-1,6-Pase structures, the tetrameric assembly of all these structures deviates from the canonical R- or T-states, representing novel tetrameric assemblies. Intriguingly, the concentration of AMP required for 50% inhibition of the Q32R mutant is increased 19-fold, and the cooperativity of both AMP and Mg2+ is abolished or decreased. These structures demonstrate the Q32R mutation affects the conformations of both N-terminal residues and the dynamic loop 52-72. Also importantly, structural comparison indicates that this mutation in helix alpha2 is detrimental to the R-to-T conversion as evidenced by the absence of quaternary structural changes upon AMP binding, providing direct evidence for the critical role of helix alpha2 in the allosteric signal transduction. Crystal Structures of Human Muscle Fructose-1,6-Bisphosphatase: Novel Quaternary States, Enhanced AMP Affinity, and Allosteric Signal Transmission Pathway.,Shi R, Chen ZY, Zhu DW, Li C, Shan Y, Xu G, Lin SX PLoS One. 2013 Sep 27;8(9):e71242. PMID:24086250[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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