|
|
| (12 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| - | [[Image:2akz.gif|left|200px]] | |
| | | | |
| - | {{Structure
| + | ==Fluoride Inhibition of Enolase: Crystal Structure of the Inhibitory Complex== |
| - | |PDB= 2akz |SIZE=350|CAPTION= <scene name='initialview01'>2akz</scene>, resolution 1.36Å
| + | <StructureSection load='2akz' size='340' side='right'caption='[[2akz]], [[Resolution|resolution]] 1.36Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=F:FLUORIDE+ION'>F</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene> | + | <table><tr><td colspan='2'>[[2akz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AKZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AKZ FirstGlance]. <br> |
| - | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphopyruvate_hydratase Phosphopyruvate hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.11 4.2.1.11] </span>
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.36Å</td></tr> |
| - | |GENE= ENO2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F:FLUORIDE+ION'>F</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr> |
| - | |DOMAIN=
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2akz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2akz OCA], [https://pdbe.org/2akz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2akz RCSB], [https://www.ebi.ac.uk/pdbsum/2akz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2akz ProSAT]</span></td></tr> |
| - | |RELATEDENTRY=[[1te6|1TE6]], [[2akm|2AKM]]
| + | </table> |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2akz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2akz OCA], [http://www.ebi.ac.uk/pdbsum/2akz PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2akz RCSB]</span>
| + | == Function == |
| - | }}
| + | [https://www.uniprot.org/uniprot/ENOG_HUMAN ENOG_HUMAN] Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell survival (By similarity). |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ak/2akz_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2akz ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | '''Fluoride Inhibition of Enolase: Crystal Structure of the Inhibitory Complex'''
| + | ==See Also== |
| - | | + | *[[Enolase 3D structures|Enolase 3D structures]] |
| - | | + | __TOC__ |
| - | ==Overview== | + | </StructureSection> |
| - | Enolase is a dimeric metal-activated metalloenzyme which uses two magnesium ions per subunit: the strongly bound conformational ion and the catalytic ion that binds to the enzyme-substrate complex inducing catalysis. The crystal structure of the human neuronal enolase-Mg2F2P(i) complex (enolase fluoride/phosphate inhibitory complex, EFPIC) determined at 1.36 A resolution shows that the combination of anions effectively mimics an intermediate state in catalysis. The phosphate ion binds in the same site as the phosphate group of the substrate/product, 2-phospho-D-glycerate/phosphoenolpyruvate, and induces binding of the catalytic Mg2+ ion. One fluoride ion bridges the structural and catalytic magnesium ions while the other interacts with the structural magnesium ion and the ammonio groups of Lys 342 and Lys 393. These fluoride ion positions correspond closely to the positions of the oxygen atoms of the substrate's carboxylate moiety. To relate structural changes resulting from fluoride, phosphate, and magnesium ions binding to those that are induced by phosphate and magnesium ions alone, we also determined the structure of the human neuronal enolase-Mg2P(i) complex (enolase phosphate inhibitory complex, EPIC) at 1.92 A resolution. It shows the closed conformation in one subunit and a mixture of open and semiclosed conformations in the other. The EPFIC dimer is essentially symmetric while the EPIC dimer is asymmetric. Isothermal titration calorimetry data confirmed binding of four fluoride ions per dimer and yielded Kb values of 7.5 x 10(5) +/- 1.3 x 10(5), 1.2 x 10(5) +/- 0.2 x 10(5), 8.6 x 10(4) +/- 1.6 x 10(4), and 1.6 x 10(4) +/- 0.7 x 10(4) M(-1). The different binding constants indicate negative cooperativity between the subunits; the asymmetry of EPIC supports such an interpretation.
| + | |
| - | | + | |
| - | ==About this Structure==
| + | |
| - | 2AKZ is a [[Single protein]] structure of 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=2AKZ OCA].
| + | |
| - | | + | |
| - | ==Reference==
| + | |
| - | Fluoride inhibition of enolase: crystal structure and thermodynamics., Qin J, Chai G, Brewer JM, Lovelace LL, Lebioda L, Biochemistry. 2006 Jan 24;45(3):793-800. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16411755 16411755]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Phosphopyruvate hydratase]] | + | [[Category: Large Structures]] |
| - | [[Category: Single protein]]
| + | [[Category: Brewer JM]] |
| - | [[Category: Brewer, J M.]] | + | [[Category: Chai G]] |
| - | [[Category: Chai, G.]] | + | [[Category: Lovelace LL]] |
| - | [[Category: Lovelace, L L.]] | + | [[Category: Qin J]] |
| - | [[Category: Qin, J.]] | + | |
| - | [[Category: crystal structure]]
| + | |
| - | [[Category: enolase]]
| + | |
| - | [[Category: fluoride inhibition]]
| + | |
| - | [[Category: glycolysis]]
| + | |
| - | [[Category: isothermal titration calorimetry]]
| + | |
| - | [[Category: negative cooperativity]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:54:00 2008''
| + | |
