1fta

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /> <applet load="1fta" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fta, resolution 2.3&Aring;" /> '''FRUCTOSE-1,6-BISPHOS...)
Current revision (07:19, 7 February 2024) (edit) (undo)
 
(18 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1fta.gif|left|200px]]<br />
 
-
<applet load="1fta" size="450" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1fta, resolution 2.3&Aring;" />
 
-
'''FRUCTOSE-1,6-BISPHOSPHATASE(D-FRUCTOSE-1,6-BISPHOSPHATE, 1-PHOSPHOHYDROLASE) (E.C.3.1.3.11) COMPLEXED WITH THE ALLOSTERIC INHIBITOR AMP'''<br />
 
-
==Overview==
+
==FRUCTOSE-1,6-BISPHOSPHATASE(D-FRUCTOSE-1,6-BISPHOSPHATE, 1-PHOSPHOHYDROLASE) (E.C.3.1.3.11) COMPLEXED WITH THE ALLOSTERIC INHIBITOR AMP==
-
The molecular structure of human liver fructose-1,6-bisphosphatase, complexed with AMP was determined by x-ray diffraction using molecular, replacement, starting from the pig kidney enzyme AMP complex. Of the 34, amino acid residues which differ between these two sequences, only one, interacts with AMP; Met30 in pig kidney is Leu30 in human liver. From this, analysis, six sites in which side chains of amino acid residues are in, contact with AMP, Ala24, Leu30, Thr31, Tyr113, Arg140, and Met177, were, mutated by polymerase chain reaction. The wild-type and mutant forms were, expressed in Escherichia coli, purified, and their kinetic properties, determined. Circular dichroism spectra of the mutants were, indistinguishable from that of the wild-type enzyme. Kinetic analyses, revealed that all forms had similar turnover numbers, Km values for, fructose 2,6-bisphosphate, and inhibition constants for fructose, 2,6-bisphosphate. Apparent Ki values for AMP inhibition of the Leu30 --&gt;, Phe and Met177 --&gt; Ala mutants were similar to those of the wild-type, enzyme, but the apparent Ki values for the Arg140 --&gt; Ala and Ala24 --&gt;, Phe mutants were 7-to 20-fold higher, respectively. The Thr31 --&gt; Ser, mutant exhibited a 5-fold increase in apparent Ki for AMP, while mutation, of Thr31 to Ala increased the apparent Ki 120-fold. AMP inhibition of the, Tyr113 --&gt; Phe mutant was undetectable even at millimolar AMP, concentrations. Fructose 2,6-bisphosphate potentiated AMP inhibition of, the mutants to the same extent as for the wild-type enzyme, except in the, case of the Thr31 --&gt; Ala and Tyr113 --&gt; Phe mutants. Thus, the Met177 --&gt;, Ala mutant suggests that the side chain beyond C alpha is not needed for, AMP binding, and that the Leu30 --&gt; Phe mutant preserves the AMP contacts, with these side chains. Thr31, Tyr113, and Arg140 form key hydrogen bonds, to AMP consistent with strong side chain interactions in the wild-type, enzyme. Finally, the absence of any effect of fructose 2,6-bisphosphate on, AMP inhibition observed in the Thr31 --&gt; Ala mutant may be an important, clue relating to the mechanism of synergism of these two inhibitors.
+
<StructureSection load='1fta' size='340' side='right'caption='[[1fta]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1fta]] is a 4 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=1FTA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FTA 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]] 2.3&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</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=1fta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fta OCA], [https://pdbe.org/1fta PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fta RCSB], [https://www.ebi.ac.uk/pdbsum/1fta PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fta ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/F16P1_HUMAN F16P1_HUMAN] Defects in FBP1 are the cause of fructose-1,6-bisphosphatase deficiency (FBPD) [MIM:[https://omim.org/entry/229700 229700]. FBPD is inherited as an autosomal recessive disorder mainly in the liver and causes life-threatening episodes of hypoglycemia and metabolic acidosis (lactacidemia) in newborn infants or young children.<ref>PMID:9382095</ref> <ref>PMID:12126934</ref>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/F16P1_HUMAN F16P1_HUMAN]
 +
== 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/ft/1fta_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=1fta ConSurf].
 +
<div style="clear:both"></div>
-
==Disease==
+
==See Also==
-
Known diseases associated with this structure: Fructose-bisphosphatase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=229700 229700]]
+
*[[Fructose-1%2C6-bisphosphatase 3D structures|Fructose-1%2C6-bisphosphatase 3D structures]]
-
 
+
== References ==
-
==About this Structure==
+
<references/>
-
1FTA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with AMP as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FTA OCA].
+
__TOC__
-
 
+
</StructureSection>
-
==Reference==
+
-
The allosteric site of human liver fructose-1,6-bisphosphatase. Analysis of six AMP site mutants based on the crystal structure., Gidh-Jain M, Zhang Y, van Poelje PD, Liang JY, Huang S, Kim J, Elliott JT, Erion MD, Pilkis SJ, Raafat el-Maghrabi M, et al., J Biol Chem. 1994 Nov 4;269(44):27732-8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7961695 7961695]
+
-
[[Category: Fructose-bisphosphatase]]
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Single protein]]
+
[[Category: Large Structures]]
-
[[Category: Huang, S.]]
+
[[Category: Huang S]]
-
[[Category: Liang, J.Y.]]
+
[[Category: Liang J-Y]]
-
[[Category: Lipscomb, W.N.]]
+
[[Category: Lipscomb WN]]
-
[[Category: Zhang, Y.]]
+
[[Category: Zhang Y]]
-
[[Category: AMP]]
+
-
[[Category: hydrolase (phosphoric monoester)]]
+
-
 
+
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:57:19 2007''
+

Current revision

FRUCTOSE-1,6-BISPHOSPHATASE(D-FRUCTOSE-1,6-BISPHOSPHATE, 1-PHOSPHOHYDROLASE) (E.C.3.1.3.11) COMPLEXED WITH THE ALLOSTERIC INHIBITOR AMP

PDB ID 1fta

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1fta"
Personal tools