This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


1dhj

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (06:53, 7 February 2024) (edit) (undo)
 
(18 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1dhj.gif|left|200px]]<br /><applet load="1dhj" size="350" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1dhj, resolution 1.8&Aring;" />
 
-
'''LONG-RANGE STRUCTURAL EFFECTS IN A SECOND-SITE REVERTANT OF A MUTANT DIHYDROFOLATE REDUCTASE'''<br />
 
-
==Overview==
+
==LONG-RANGE STRUCTURAL EFFECTS IN A SECOND-SITE REVERTANT OF A MUTANT DIHYDROFOLATE REDUCTASE==
-
X-ray crystal structures have been determined for a second-site revertant (Asp-27--&gt;Ser, Phe-137--&gt;Ser; D27S/F137S) and both component single-site mutants of Escherichia coli dihydrofolate reductase. The primary D27S mutation, located in the substrate binding pocket, greatly reduces catalytic activity as compared to the wild-type enzyme. The additional F137S mutation, which partially restores catalytic activity, is located on the surface of the molecule, well outside of the catalytic center and approximately 15 A from residue 27. Comparison of kinetic data for the single-site F137S mutant, specifically constructed as a control, and for the double-mutant enzymes indicates that the effects of the F137S and D27S mutations on catalysis are nonadditive. This result suggests that the second-site mutation might mediate its effects through a structural perturbation propagated along the polypeptide backbone. To investigate the mechanism by which the F137S substitution elevates the catalytic activity of D27S we have determined the structure of the D27S/F137S double mutant. We also present a rerefined structure for the original D27S mutant and a preliminary structural interpretation for the F137S single-site mutant. We find that while either single mutant shows little more than a simple side-chain substitution, the double mutant undergoes an extended structural perturbation, which is propagated between these two widely separated sites via the helix alpha B.
+
<StructureSection load='1dhj' size='340' side='right'caption='[[1dhj]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1dhj]] 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=1DHJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DHJ 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]] 1.8&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MTX:METHOTREXATE'>MTX</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=1dhj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dhj OCA], [https://pdbe.org/1dhj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dhj RCSB], [https://www.ebi.ac.uk/pdbsum/1dhj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dhj ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/DYR_ECOLI DYR_ECOLI] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
 +
== 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/dh/1dhj_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=1dhj ConSurf].
 +
<div style="clear:both"></div>
-
==About this Structure==
+
==See Also==
-
1DHJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=MTX:'>MTX</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DHJ OCA].
+
*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]]
-
 
+
__TOC__
-
==Reference==
+
</StructureSection>
-
Long-range structural effects in a second-site revertant of a mutant dihydrofolate reductase., Brown KA, Howell EE, Kraut J, Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11753-6. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8265622 8265622]
+
-
[[Category: Dihydrofolate reductase]]
+
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
-
[[Category: Single protein]]
+
[[Category: Large Structures]]
-
[[Category: Brown, K A.]]
+
[[Category: Brown KA]]
-
[[Category: Kraut, J.]]
+
[[Category: Kraut J]]
-
[[Category: CA]]
+
-
[[Category: CL]]
+
-
[[Category: MTX]]
+
-
[[Category: oxidoreductase]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:16:39 2008''
+

Current revision

LONG-RANGE STRUCTURAL EFFECTS IN A SECOND-SITE REVERTANT OF A MUTANT DIHYDROFOLATE REDUCTASE

PDB ID 1dhj

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/1dhj"
Personal tools