2rk8: Difference between revisions

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New page: left|200px<br /><applet load="2rk8" size="350" color="white" frame="true" align="right" spinBox="true" caption="2rk8, resolution 2.000Å" /> '''The Structure of ra...
 
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[[Image:2rk8.jpg|left|200px]]<br /><applet load="2rk8" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2rk8, resolution 2.000&Aring;" />
'''The Structure of rat cytosolic PEPCK in complex with phosphonoformate'''<br />


==Overview==
==The Structure of rat cytosolic PEPCK in complex with phosphonoformate==
The mechanisms of molecular recognition of phosphoenolpyruvate (PEP) and, oxaloacetate (OAA) by cytosolic phosphoenolpyruvate carboxykinase (cPEPCK), were investigated by the systematic evaluation of a variety of PEP and OAA, analogues as potential reversible inhibitors of the enzyme against PEP., The molecules that inhibit the enzyme in a competitive fashion were found, to fall into two general classes. Those molecules that mimic the binding, geometry of PEP, namely phosphoglycolate and 3-phosphonopropionate, are, found to bind weakly (millimolar Ki values). In contrast, those, competitive inhibitors that mimic the binding of OAA (oxalate and, phosphonoformate) coordinate directly to the active site manganese ion and, bind an order of magnitude more tightly (micromolar Ki values). The, competitive inhibitor sulfoacetate is found to be an outlier of these two, classes, binding in a hybrid fashion utilizing modes of recognition of, both PEP and OAA in order to achieve a micromolar inhibition constant in, the absence of direct coordination to the active site metal. The kinetic, studies in combination with the structural characterization of the five, aforementioned competitive inhibitors demonstrate the molecular, requirements for high affinity binding of molecules to the active site of, the enzyme. These features include cis-planar carbonyl groups that are, required for coordination to the active site metal, a bridging electron, rich atom at the position corresponding to the C2 methylene group of OAA, to facilitate interactions with R405, a carboxylate or sulfonate moiety at, a position corresponding to the C1 carboxylate of OAA, and the edge-on, aromatic interaction between a carboxylate and Y235.
<StructureSection load='2rk8' size='340' side='right'caption='[[2rk8]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2rk8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RK8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RK8 FirstGlance]. <br>
</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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PPF:PHOSPHONOFORMIC+ACID'>PPF</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2rk8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rk8 OCA], [https://pdbe.org/2rk8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rk8 RCSB], [https://www.ebi.ac.uk/pdbsum/2rk8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rk8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PCKGC_RAT PCKGC_RAT] Catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle.
== 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/rk/2rk8_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=2rk8 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
2RK8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=MN:'>MN</scene>, <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=PPF:'>PPF</scene>, <scene name='pdbligand=FMT:'>FMT</scene> and <scene name='pdbligand=PEG:'>PEG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphoenolpyruvate_carboxykinase_(GTP) Phosphoenolpyruvate carboxykinase (GTP)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.32 4.1.1.32] Known structural/functional Sites: <scene name='pdbsite=AC1:Mn Binding Site For Residue A 700'>AC1</scene>, <scene name='pdbsite=AC2:Na Binding Site For Residue A 624'>AC2</scene>, <scene name='pdbsite=AC3:Mn Binding Site For Residue B 700'>AC3</scene>, <scene name='pdbsite=AC4:Na Binding Site For Residue B 624'>AC4</scene>, <scene name='pdbsite=AC5:Ppf Binding Site For Residue A 3969'>AC5</scene>, <scene name='pdbsite=AC6:Ppf Binding Site For Residue B 3969'>AC6</scene>, <scene name='pdbsite=AC7:Fmt Binding Site For Residue A 3406'>AC7</scene>, <scene name='pdbsite=AC8:Peg Binding Site For Residue A 5759'>AC8</scene> and <scene name='pdbsite=AC9:Fmt Binding Site For Residue B 3406'>AC9</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RK8 OCA].
*[[Phosphoenolpyruvate carboxykinase 3D structures|Phosphoenolpyruvate carboxykinase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
Differential Inhibition of Cytosolic PEPCK by Substrate Analogues. Kinetic and Structural Characterization of Inhibitor Recognition., Stiffin RM, Sullivan SM, Carlson GM, Holyoak T, Biochemistry. 2008 Jan 16;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18197707 18197707]
[[Category: Large Structures]]
[[Category: Phosphoenolpyruvate carboxykinase (GTP)]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Single protein]]
[[Category: Carlson GM]]
[[Category: Carlson, G.M.]]
[[Category: Holyoak T]]
[[Category: Holyoak, T.]]
[[Category: Stiffin RM]]
[[Category: Stiffin, R.M.]]
[[Category: Sullivan SM]]
[[Category: Sullivan, S.M.]]
[[Category: FMT]]
[[Category: MN]]
[[Category: NA]]
[[Category: PEG]]
[[Category: PPF]]
[[Category: cytoplasm]]
[[Category: decarboxylase]]
[[Category: gluconeogenesis]]
[[Category: gtp-binding]]
[[Category: kinase]]
[[Category: lyase]]
[[Category: nucleotide-binding]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jan 31 11:00:49 2008''

Latest revision as of 12:22, 21 February 2024

The Structure of rat cytosolic PEPCK in complex with phosphonoformateThe Structure of rat cytosolic PEPCK in complex with phosphonoformate

Structural highlights

2rk8 is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2Å
Ligands:, , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PCKGC_RAT Catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

2rk8, resolution 2.00Å

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