Three new crystal structures of point mutation variants of monoTIM: conformational flexibility of loop-1, loop-4 and loop-8

Structure
T V BorchertR K Wierenga

Abstract

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. 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. 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 simil...Continue Reading

References

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Citations

Feb 1, 1996·Protein Science : a Publication of the Protein Society·W SchliebsR Wierenga
Apr 7, 2007·AIDS Research and Human Retroviruses·Timothy CardozoSusan Zolla-Pazner
Aug 6, 2014·Bioorganic Chemistry·John P RichardM Merced Malabanan
Aug 10, 2010·Cellular and Molecular Life Sciences : CMLS·R K WierengaR Venkatesan
Jan 22, 2000·Computers & Chemistry·T CardozoR Abagyan
Jul 12, 2007·Proteins·Tulika PrakashSamir K Brahmachari
Dec 10, 2013·Protein Science : a Publication of the Protein Society·Ataur R Katebi, Robert L Jernigan
Mar 15, 2015·Protein Engineering, Design & Selection : PEDS·Mirja KrauseRik K Wierenga
Nov 14, 2007·Structure·Emmanuel D Levy
Aug 10, 2010·Acta Crystallographica. Section D, Biological Crystallography·Mikko SalinRik K Wierenga
Dec 1, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Alejandra Vázquez-RaygozaAlfredo Téllez-Valencia
May 2, 2002·Protein Engineering·K V BrindaS Vishveshwara
Oct 13, 2009·Journal of Chemical Theory and Computation·Chai Ann NgRobert T C Brownlee

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