|
|
| (14 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| - | [[Image:1nxg.gif|left|200px]] | |
| | | | |
| - | <!-- | + | ==The F383A variant of type II Citrate Synthase complexed with NADH== |
| - | The line below this paragraph, containing "STRUCTURE_1nxg", creates the "Structure Box" on the page.
| + | <StructureSection load='1nxg' size='340' side='right'caption='[[1nxg]], [[Resolution|resolution]] 2.50Å' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[1nxg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NXG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NXG FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | {{STRUCTURE_1nxg| PDB=1nxg | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nxg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nxg OCA], [https://pdbe.org/1nxg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nxg RCSB], [https://www.ebi.ac.uk/pdbsum/1nxg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nxg ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/CISY_ECOLI CISY_ECOLI] |
| | + | == 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/nx/1nxg_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=1nxg ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | '''The F383A variant of type II Citrate Synthase complexed with NADH'''
| + | ==See Also== |
| - | | + | *[[Citrate Synthase 3D structures|Citrate Synthase 3D structures]] |
| - | | + | __TOC__ |
| - | ==Overview== | + | </StructureSection> |
| - | Study of the hexameric and allosterically regulated citrate synthases (type II CS) provides a rare opportunity to gain not only an understanding of a novel allosteric mechanism but also insight into how such properties can evolve from an unregulated structural platform (the dimeric type I CS). To address both of these issues, we have determined the structure of the complex of NADH (a negative allosteric effector) with the F383A variant of type II Escherichia coli CS. This variant was chosen because its kinetics indicate it is primarily in the T or inactive allosteric conformation, the state that strongly binds to NADH. Our structural analyses show that the six NADH binding sites in the hexameric CS complex are located at the interfaces between dimer units such that most of each site is formed by one subunit, but a number of key residues are drawn from the adjacent dimer. This arrangement of interactions serves to explain why NADH allosteric regulation is a feature only of hexameric type II CS. Surprisingly, in both the wild-type enzyme and the NADH complex, the two subunits of each dimer within the hexameric conformation are similar but not identical in structure, and therefore, while the general characteristics of NADH binding interactions are similar in each subunit, the details of these are somewhat different between subunits. Detailed examination of the observed NADH binding sites indicates that both direct charged interactions and the overall cationic nature of the sites are likely responsible for the ability of these sites to discriminate between NADH and NAD(+). A particularly novel characteristic of the complex is the horseshoe conformation assumed by NADH, which is strikingly different from the extended conformation found in its complexes with most proteins. Sequence homology studies suggest that this approach to binding NADH may arise out of the evolutionary need to add an allosteric regulatory function to the base CS structure. Comparisons of the amino acid sequences of known type II CS enzymes, from different Gram-negative bacteria taxonomic groups, show that the NADH-binding residues identified in our structure are strongly conserved, while hexameric CS molecules that are insensitive to NADH have undergone key changes in the sequence of this part of the protein.
| + | |
| - | | + | |
| - | ==About this Structure==
| + | |
| - | 1NXG is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NXG OCA].
| + | |
| - | | + | |
| - | ==Reference==
| + | |
| - | Insights into the evolution of allosteric properties. The NADH binding site of hexameric type II citrate synthases., Maurus R, Nguyen NT, Stokell DJ, Ayed A, Hultin PG, Duckworth HW, Brayer GD, Biochemistry. 2003 May 20;42(19):5555-65. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12741811 12741811]
| + | |
| | [[Category: Escherichia coli]] | | [[Category: Escherichia coli]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Ayed, A.]] | + | [[Category: Ayed A]] |
| - | [[Category: Brayer, G D.]] | + | [[Category: Brayer GD]] |
| - | [[Category: Duckworth, H W.]] | + | [[Category: Duckworth HW]] |
| - | [[Category: Hultin, P G.]] | + | [[Category: Hultin PG]] |
| - | [[Category: Maurus, R.]] | + | [[Category: Maurus R]] |
| - | [[Category: Nguyen, N T.]] | + | [[Category: Nguyen NT]] |
| - | [[Category: Stokell, D J.]] | + | [[Category: Stokell DJ]] |
| - | [[Category: Allosteric]]
| + | |
| - | [[Category: Citrate synthase]]
| + | |
| - | [[Category: F383a]]
| + | |
| - | [[Category: Nadh]]
| + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 03:05:40 2008''
| + | |
