Motion in Triose Phosphate Isomerase (TIM) [tim]

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Classification Known Fragment Motion, Hinge Mechanism [F-h-2]

Structures
2YPI Conformation 1 [ PartsList ]
3TIM Conformation 2 [ PartsList ]
6TIM Conformation 3 [ PartsList ]

Description
Loop closure with 2 hinges moves CA atoms ~ 7 A. Triose Phosphate Isomerase is one of the most extensively studied examples of loop closure. Three different variants of the enzyme have been analyzed crystallographically (chicken, yeast, and trypanosome) and the enzyme has been solved in both open and closed conformations. The loop closure has also been studied by techniques ranging from site-directed mutagenesis to molecular dynamics. TIM is a beta-barrel enzyme that contains 8 helices packed onto a barrel of 8 sheets. An 11-residue loop running from an inner strand to an outer helix is flexible. When the enzyme binds its substrate the loop closes over the active site, shielding the substrate from water. The loop appears to close as a rigid lid, stabilized by internal hydrogen bonds. Its motion involves movements of alpha carbons of up to 8 A. The closure involves the filling of a cavity near the base of the helix to which the loop is connected and the formation of new hydrogen bonds and contacts.

Particular values describing motion
Creation Date = 19970822
Modification Date = 19970822
Experimental Methods = x (Traditional x-ray)

References
T V Borchert, KV R Kishan, J P Zellen, W Schliebs, N Thanki, R Abagyan, R jaenicke, and R K Wierenga (1995). Three new crystal structures of point mutation variants of monoTIM: conformational flexibility of loop-1, loop-4 [sic] and loop-8. Structure 3:669-679. [Medline info for 93376766]
J C Williams and A E McDermott (1995). Dynamics of the Flexible Loop of Triosephosphate Isomerase: The Loop Motion is Not Ligand Gated. Biochem. 34:8309-8319. [Medline info for 93376766]
E Lolis and G A Petsko (1990). Crystallographic analysis of the complex between triosephosphate isomerase and 2-phosphoglycolate at 2.5 Å resolution: Implications for catalysis. Biochemistry. 29: 6619-25. [Medline info for 93376766]
R K Wierenga, M E M Noble, J P M Postma, H Groendijk, K H Kalk, W G J Hol and F R Opperdoes (1991). The crystal structure of the open and the closed conformation of the flexible loop of trypanosomal triosephosphate isomerase. Proteins. 10: 93. [Medline info for 93376766]
D Joseph, G A Petsko and M Karplus (1990). Anatomy of Conformational Change: Hinged Lid Motion of the Triosephosphosphate Isomerase Loop. Science. 249: 1425-1428. [Medline info for 90385280]
R K Wierenga, M E M Noble and R C Davenport (1992). Comparison of the Refined Crystal Structures of Liganded and Unliganded Chicken, Yeast and Trypanosomal Triosephosphate Isomerase. J. Mol. Biol. 224: 1115-1126. [Medline info for 91288486]

Data and Graphics
Graphic-3 Closeup of loop motion.
Graphic-2 Overall picture of flexible loop in context of fold.
Graphic-1 Overall picture of flexible loop in context of topology.

GO terms associated with structures
Molecular functiontriose-phosphate isomerase activity
Biological processmetabolism

Morphs

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Best representative
Morph Morph name Structure #1 Structure #2 Residues
TIM 6tim [ A ] 1tre [ A ] 255

User-submitted morphs
Morph Morph name Structure #1 Structure #2 Residues
04407-13635 Triose Phosphate Isomerase 1ydv [ A ] 1aw2 [ A ] 256
223417-6867 Triose Phosphate Isomerase 1ypi [ A ] 2ypi [ A ] 247
36571-1479 triosephosphate isom 1tpe [ A ] 6tim [ A ] 250


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Copyright 1995-2005 M. Gerstein, W. Krebs, S. Flores, N. Echols, and others
Email: Mark.Gerstein _at_ yale.edu