2v2h: Difference between revisions

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Activity:

Triose-phosphate isomerase, with EC number 5.3.1.1

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THE A178L MUTATION IN THE C-TERMINAL HINGE OF THE FLEXIBLE LOOP-6 OF TRIOSEPHOSPHATE ISOMERASE (TIM) INDUCES A MORE CLOSED CONFORMATION OF THIS HINGE REGION IN DIMERIC AND MONOMERIC TIM

OverviewOverview

The flexible catalytic loop, loop-6, of TIM has evolved to preferably be open in the unliganded state and to preferably be closed in the liganded state. The N-terminal and C-terminal hinges of this loop are important for its opening/closing mechanism. In this study, a small conserved C-terminal hinge residue, Ala178, has been mutated into a residue with a larger side chain, Leu178. This mutation has been made in the dimeric trypanosomal wild-type TIM (wtTIM) and in its mutated catalytically competent monomeric variant (ml1TIM). The variants are referred to as A178L and ml1A178L, respectively. Crystal structures have been determined of unliganded A178L (at 2.2 A), liganded A178L (at 1.89 A), unliganded ml1A178L (at 2.3 A) and liganded ml1A178L (at 1.18 A) using the transition-state analogue 2-phosphoglycolate as a ligand. Structural characterization of the two variants shows that this mutation favours the closed conformation of the C-terminal hinge region, even in the absence of ligand. In the structure of the unliganded A178L variant a range of new loop-6 conformations are observed, including subunits in which the tip of loop-6 is completely disordered. The catalytic efficiency of A178L is lower than that of wtTIM, which correlates with the structural differences between the apo forms of wtTIM and A178L, in particular the more disordered loop-6 in the structure of unliganded A178L. In the liganded structures of A178L and ml1A178L the structural differences induced by the mutation are minimal. Structural characterization of the ml1A178L variant highlights its structural plasticity.

About this StructureAbout this Structure

2V2H is a Single protein structure of sequence from Trypanosoma brucei brucei. Full crystallographic information is available from OCA.

ReferenceReference

Structural studies show that the A178L mutation in the C-terminal hinge of the catalytic loop-6 of triosephosphate isomerase (TIM) induces a closed-like conformation in dimeric and monomeric TIM., Alahuhta M, Casteleijn MG, Neubauer P, Wierenga RK, Acta Crystallogr D Biol Crystallogr. 2008 Feb;64(Pt 2):178-88. Epub 2008, Jan 16. PMID:18219118

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@@ Line 1: / Line 1: @@
-[[Image:2v2h.jpg|left|200px]]<br /><applet load="2v2h" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:2v2h.jpg|left|200px]]
-caption="2v2h, resolution 1.18&Aring;" />
-'''THE A178L MUTATION IN THE C-TERMINAL HINGE OF THE FLEXIBLE LOOP-6 OF TRIOSEPHOSPHATE ISOMERASE (TIM) INDUCES A MORE CLOSED CONFORMATION OF THIS HINGE REGION IN DIMERIC AND MONOMERIC TIM'''<br />
+ {{Structure
+|PDB= 2v2h |SIZE=350|CAPTION= <scene name='initialview01'>2v2h</scene>, resolution 1.18&Aring;
+|SITE= <scene name='pdbsite=AC1:Pga+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:Pga+Binding+Site+For+Chain+B'>AC2</scene>, <scene name='pdbsite=AC3:Pga+Binding+Site+For+Chain+C'>AC3</scene>, <scene name='pdbsite=AC4:Cl+Binding+Site+For+Chain+C'>AC4</scene>, <scene name='pdbsite=AC5:Cl+Binding+Site+For+Chain+B'>AC5</scene> and <scene name='pdbsite=AC6:Cl+Binding+Site+For+Chain+A'>AC6</scene>
+|LIGAND= <scene name='pdbligand=PGA:2-PHOSPHOGLYCOLIC+ACID'>PGA</scene> and <scene name='pdbligand=CL:CHLORIDE ION'>CL</scene>
+|ACTIVITY= [http://en.wikipedia.org/wiki/Triose-phosphate_isomerase Triose-phosphate isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.1.1 5.3.1.1]
+|GENE=
+}}
+'''THE A178L MUTATION IN THE C-TERMINAL HINGE OF THE FLEXIBLE LOOP-6 OF TRIOSEPHOSPHATE ISOMERASE (TIM) INDUCES A MORE CLOSED CONFORMATION OF THIS HINGE REGION IN DIMERIC AND MONOMERIC TIM'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-V2H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei Trypanosoma brucei brucei] with <scene name='pdbligand=PGA:'>PGA</scene> and <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Triose-phosphate_isomerase Triose-phosphate isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.1.1 5.3.1.1] Known structural/functional Sites: <scene name='pdbsite=AC1:Pga+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:Pga+Binding+Site+For+Chain+B'>AC2</scene>, <scene name='pdbsite=AC3:Pga+Binding+Site+For+Chain+C'>AC3</scene>, <scene name='pdbsite=AC4:Cl+Binding+Site+For+Chain+C'>AC4</scene>, <scene name='pdbsite=AC5:Cl+Binding+Site+For+Chain+B'>AC5</scene> and <scene name='pdbsite=AC6:Cl+Binding+Site+For+Chain+A'>AC6</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V2H OCA].
+V2H is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei Trypanosoma brucei brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V2H OCA].
 ==Reference==
-Structural studies show that the A178L mutation in the C-terminal hinge of the catalytic loop-6 of triosephosphate isomerase (TIM) induces a closed-like conformation in dimeric and monomeric TIM., Alahuhta M, Casteleijn MG, Neubauer P, Wierenga RK, Acta Crystallogr D Biol Crystallogr. 2008 Feb;64(Pt 2):178-88. Epub 2008, Jan 16. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18219118 18219118]
+Structural studies show that the A178L mutation in the C-terminal hinge of the catalytic loop-6 of triosephosphate isomerase (TIM) induces a closed-like conformation in dimeric and monomeric TIM., Alahuhta M, Casteleijn MG, Neubauer P, Wierenga RK, Acta Crystallogr D Biol Crystallogr. 2008 Feb;64(Pt 2):178-88. Epub 2008, Jan 16. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18219118 18219118]
 [[Category: Single protein]]
 [[Category: Triose-phosphate isomerase]]
@@ Line 41: / Line 50: @@
 [[Category: triosephosphate isomerase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:52:49 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:42:40 2008''