Triose Phosphate Isomerase Structure & Mechanism
From Proteopedia
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==Triose Phosphate Isomerase (TIM)== | ==Triose Phosphate Isomerase (TIM)== | ||
| - | Triose phosphate isomerase (TIM)<ref>PMID:16511037</ref> (PDB [[1wyi]]) is a crucial enzyme in the glycolytic pathway. <scene name='Christian_Krenk_Sandbox/Nc_rainbow/1'>TIM</scene> reversibly converts the aldose Glyceraldehyde-3-phosphate (GAP) to the ketose Dihydroxyacetone phosphate (DHAP). The interconversion proceeds by an enediol intermediate. | + | Triose phosphate isomerase (TIM)<ref>PMID:16511037</ref><ref>PMID:8061610</ref> (PDB [[1wyi]] and [[1hti]]) is a crucial enzyme in the glycolytic pathway. <scene name='Christian_Krenk_Sandbox/Nc_rainbow/1'>TIM</scene> reversibly converts the aldose Glyceraldehyde-3-phosphate (GAP) to the ketose Dihydroxyacetone phosphate (DHAP). The interconversion proceeds by an enediol intermediate. |
==Structural Characteristics of TIM== | ==Structural Characteristics of TIM== | ||
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The enzyme aids in catalysis by binding tightly to the enediol transition state. To convert GAP to the enediol intermediate, a proton is abstracted from C2 by a base and the carbonyl oxygen atom is protonated by an acid. | The enzyme aids in catalysis by binding tightly to the enediol transition state. To convert GAP to the enediol intermediate, a proton is abstracted from C2 by a base and the carbonyl oxygen atom is protonated by an acid. | ||
| - | <scene name='Christian_Krenk_Sandbox/Active_site/1'> Glu 165 acts as the base and grabs the C2 proton on glyceraldehyde-3-phosphate, while His 95 is H-bonded to the carbonyl oxygen and acts as the acid by protonating carbonyl oxygen.</scene> The enediol intermediate is negatively charged, but is somewhat <scene name='Christian_Krenk_Sandbox/Lysine/1'>stabilized by the positively charged side chain of Lys 12.</scene> To convert the enediol intermediate to DHAP, C1 is protonated by Glu 165, with His 95 removing a proton from C2’s OH group. As a result, the catalytic groups are back | + | <scene name='Christian_Krenk_Sandbox/Active_site/1'> Glu 165 acts as the base and grabs the C2 proton on glyceraldehyde-3-phosphate, while His 95 is H-bonded to the carbonyl oxygen and acts as the acid by protonating carbonyl oxygen.</scene> The enediol intermediate is negatively charged, but is somewhat <scene name='Christian_Krenk_Sandbox/Lysine/1'>stabilized by the positively charged side chain of Lys 12.</scene> To convert the enediol intermediate to DHAP, C1 is protonated by Glu 165, with His 95 removing a proton from C2’s OH group. As a result, the catalytic groups are back to their original states, and catalysis is complete. |
Revision as of 20:27, 1 March 2010
Contents |
Triose Phosphate Isomerase (TIM)
Triose phosphate isomerase (TIM)[1][2] (PDB 1wyi and 1hti) is a crucial enzyme in the glycolytic pathway. reversibly converts the aldose Glyceraldehyde-3-phosphate (GAP) to the ketose Dihydroxyacetone phosphate (DHAP). The interconversion proceeds by an enediol intermediate.
Structural Characteristics of TIM
The secondary structure consists of 14 alpha helices and 8 beta sheets per monomer, making it fall in the SCOP category of alpha and beta proteins. The tertiary structure is a The quaternary structure is a homodimer.
Mechanism of TIM
The enzyme aids in catalysis by binding tightly to the enediol transition state. To convert GAP to the enediol intermediate, a proton is abstracted from C2 by a base and the carbonyl oxygen atom is protonated by an acid. The enediol intermediate is negatively charged, but is somewhat To convert the enediol intermediate to DHAP, C1 is protonated by Glu 165, with His 95 removing a proton from C2’s OH group. As a result, the catalytic groups are back to their original states, and catalysis is complete.
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| 1wyi, resolution 2.20Å () | |||||||||
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| Activity: | Triose-phosphate isomerase, with EC number 5.3.1.1 | ||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
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| 1hti, resolution 2.80Å () | |||||||||
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| Ligands: | |||||||||
| Activity: | Triose-phosphate isomerase, with EC number 5.3.1.1 | ||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
References
- ↑ Kinoshita T, Maruki R, Warizaya M, Nakajima H, Nishimura S. Structure of a high-resolution crystal form of human triosephosphate isomerase: improvement of crystals using the gel-tube method. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Apr 1;61(Pt, 4):346-9. Epub 2005 Mar 24. PMID:16511037 doi:10.1107/S1744309105008341
- ↑ Mande SC, Mainfroid V, Kalk KH, Goraj K, Martial JA, Hol WG. Crystal structure of recombinant human triosephosphate isomerase at 2.8 A resolution. Triosephosphate isomerase-related human genetic disorders and comparison with the trypanosomal enzyme. Protein Sci. 1994 May;3(5):810-21. PMID:8061610
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