Proteopedia

3gar: Difference between revisions

← Older edit
No edit summary
No edit summary
 
(11 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:3gar.jpg|left|200px]]


{{Structure
==A PH-DEPENDENT STABLIZATION OF AN ACTIVE SITE LOOP OBSERVED FROM LOW AND HIGH PH CRYSTAL STRUCTURES OF MUTANT MONOMERIC GLYCINAMIDE RIBONUCLEOTIDE TRANSFORMYLASE==
|PDB= 3gar |SIZE=350|CAPTION= <scene name='initialview01'>3gar</scene>, resolution 1.9&Aring;
<StructureSection load='3gar' size='340' side='right'caption='[[3gar]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
|SITE= <scene name='pdbsite=E70:Single+Mutation+Disrupts+The+Dimerization+Of+Gartfase'>E70</scene>
== Structural highlights ==
|LIGAND= <scene name='pdbligand=PO4:PHOSPHATE ION'>PO4</scene>
<table><tr><td colspan='2'>[[3gar]] is a 1 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=3GAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GAR FirstGlance]. <br>
|ACTIVITY= [http://en.wikipedia.org/wiki/Phosphoribosylglycinamide_formyltransferase Phosphoribosylglycinamide formyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.2.2 2.1.2.2]  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=3gar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gar OCA], [https://pdbe.org/3gar PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gar RCSB], [https://www.ebi.ac.uk/pdbsum/3gar PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gar ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PUR3_ECOLI PUR3_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/ga/3gar_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=3gar ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A mutation in the dimer interface of Escherichia coli glycinamide ribonucleotide transformylase (GarTfase) disrupts the observed pH-dependent association of the wild-type enzyme, but has no observable effect on the enzyme activity. Here, we assess whether a pH effect on the enzyme's conformation is sufficient by itself to explain the pH-dependence of the GarTfase reaction. A pH-dependent conformational change is observed between two high-resolution crystal structures of the Glu70Ala mutant GarTfase at pH 3.5 (1.8 A) and 7.5 (1.9 A). Residues 110 to 131 in GarTfase undergo a transformation from a disordered loop at pH 3.5, where the enzyme is inactive, to an ordered loop-helix structure at pH 7.5, where the enzyme is active. The ordering of this flexible loop-helix has a direct effect on catalytic residues in the active site, binding of the folate cofactor and shielding of the active site from solvent. A main-chain carbonyl oxygen atom from Tyr115 in the ordered loop forms a hydrogen bond with His108, and thereby provides electronic and structural stabilization of this key active site residue. Kinetic data indicate that the pKa of His108 is in fact raised to 9. 2. The loop movement can be correlated with elevation of the His pKa, but with further stabilization, probably from Asp144, after the binding of folate cofactor. Leu118, also in the loop, becomes positioned near the p-amino benzoic acid binding site, providing additional hydrophobic interactions with the cofactor 10-formyl tetrahydrofolate. Thus, the pH-dependence of the enzyme activity appears to arise from local active site rearrangements and not from differences due to monomer-dimer association.


'''A PH-DEPENDENT STABLIZATION OF AN ACTIVE SITE LOOP OBSERVED FROM LOW AND HIGH PH CRYSTAL STRUCTURES OF MUTANT MONOMERIC GLYCINAMIDE RIBONUCLEOTIDE TRANSFORMYLASE'''
A pH-dependent stabilization of an active site loop observed from low and high pH crystal structures of mutant monomeric glycinamide ribonucleotide transformylase at 1.8 to 1.9 A.,Su Y, Yamashita MM, Greasley SE, Mullen CA, Shim JH, Jennings PA, Benkovic SJ, Wilson IA J Mol Biol. 1998 Aug 21;281(3):485-99. PMID:9698564<ref>PMID:9698564</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3gar" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
A mutation in the dimer interface of Escherichia coli glycinamide ribonucleotide transformylase (GarTfase) disrupts the observed pH-dependent association of the wild-type enzyme, but has no observable effect on the enzyme activity. Here, we assess whether a pH effect on the enzyme's conformation is sufficient by itself to explain the pH-dependence of the GarTfase reaction. A pH-dependent conformational change is observed between two high-resolution crystal structures of the Glu70Ala mutant GarTfase at pH 3.5 (1.8 A) and 7.5 (1.9 A). Residues 110 to 131 in GarTfase undergo a transformation from a disordered loop at pH 3.5, where the enzyme is inactive, to an ordered loop-helix structure at pH 7.5, where the enzyme is active. The ordering of this flexible loop-helix has a direct effect on catalytic residues in the active site, binding of the folate cofactor and shielding of the active site from solvent. A main-chain carbonyl oxygen atom from Tyr115 in the ordered loop forms a hydrogen bond with His108, and thereby provides electronic and structural stabilization of this key active site residue. Kinetic data indicate that the pKa of His108 is in fact raised to 9. 2. The loop movement can be correlated with elevation of the His pKa, but with further stabilization, probably from Asp144, after the binding of folate cofactor. Leu118, also in the loop, becomes positioned near the p-amino benzoic acid binding site, providing additional hydrophobic interactions with the cofactor 10-formyl tetrahydrofolate. Thus, the pH-dependence of the enzyme activity appears to arise from local active site rearrangements and not from differences due to monomer-dimer association.
*[[Microtubule-associated protein 3D structures|Microtubule-associated protein 3D structures]]
 
== References ==
==About this Structure==
<references/>
3GAR 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=3GAR OCA].
__TOC__
 
</StructureSection>
==Reference==
A pH-dependent stabilization of an active site loop observed from low and high pH crystal structures of mutant monomeric glycinamide ribonucleotide transformylase at 1.8 to 1.9 A., Su Y, Yamashita MM, Greasley SE, Mullen CA, Shim JH, Jennings PA, Benkovic SJ, Wilson IA, J Mol Biol. 1998 Aug 21;281(3):485-99. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9698564 9698564]
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Phosphoribosylglycinamide formyltransferase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Benkovic SJ]]
[[Category: Benkovic, S J.]]
[[Category: Greasley SE]]
[[Category: Greasley, S E.]]
[[Category: Jennings PA]]
[[Category: Jennings, P A.]]
[[Category: Mullen CA]]
[[Category: Mullen, C A.]]
[[Category: Shim JH]]
[[Category: Shim, J H.]]
[[Category: Su Y]]
[[Category: Su, Y.]]
[[Category: Wilson IA]]
[[Category: Wilson, I A.]]
[[Category: Yamashita MM]]
[[Category: Yamashita, M M.]]
[[Category: PO4]]
[[Category: anti-cancer agent]]
[[Category: enzyme mechanism]]
[[Category: folate cofactor]]
[[Category: loop flexibility]]
[[Category: monomer-dimer association]]
[[Category: purine biosynthesis]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 19:04:52 2008''

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/w/3gar"