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1ttj
From Proteopedia
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THREE NEW CRYSTAL STRUCTURES OF POINT MUTATION VARIANTS OF MONOTIM: CONFORMATIONAL FLEXIBILITY OF LOOP-1,LOOP-4 AND LOOP-8
Overview
BACKGROUND: Wild-type triosephosphate isomerase (TIM) is a very stable, dimeric enzyme. This dimer can be converted into a stable monomeric, protein (monoTIM) by replacing the 15-residue interface loop (loop-3) by a, shorter, 8-residue, loop. The crystal structure of monoTIM shows that two, active-site loops (loop-1 and loop-4), which are at the dimer interface in, wild-type TIM, have acquired rather different structural properties., Nevertheless, monoTIM has residual catalytic activity. RESULTS: Three new, structures of variants of monoTIM are presented, a double-point mutant, crystallized in the presence and absence of bound inhibitor, and a, single-point mutant in the presence of a different inhibitor. These new, structures show large structural variability for the active-site loops, loop-1, loop-4 and loop-8. In the structures with inhibitor bound, the, catalytic lysine (Lys13 in loop-1) and the catalytic histidine (His95 in, loop-4) adopt conformations similar to those observed in wild-type TIM, but very different from the monoTIM structure. CONCLUSIONS: The residual, catalytic activity of monoTIM can now be rationalized. In the presence of, substrate analogues the active-site loops, loop-1, loop-4 and loop-8, as, well as the catalytic residues, adopt conformations similar to those seen, in the wild-type protein. These loops lack conformational flexibility in, wild-type TIM. The data suggest that the rigidity of these loops in, wild-type TIM, resulting from subunit-subunit contacts at the dimer, interface, is important for optimal catalysis.
About this Structure
1TTJ is a Single protein structure of sequence from Trypanosoma brucei brucei with PGH as ligand. Active as Triose-phosphate isomerase, with EC number 5.3.1.1 Full crystallographic information is available from OCA.
Reference
Three new crystal structures of point mutation variants of monoTIM: conformational flexibility of loop-1, loop-4 and loop-8., Borchert TV, Kishan KV, Zeelen JP, Schliebs W, Thanki N, Abagyan R, Jaenicke R, Wierenga RK, Structure. 1995 Jul 15;3(7):669-79. PMID:8591044
Page seeded by OCA on Wed Nov 21 03:34:53 2007
