We present new findings on how primary and secondary structure affects the role of fast protein motions in the reaction coordinates of enzymatic reactions. Using transition path sam- pling (TPS) and committor distribution analysis, we examined the difference in the role of these fast protein motions in the reaction coordinate of lactate dehydrogenases (LDH) of Api- complexa organisms Plasmodium falciparum and Cryptosporidium parvum.
Having evolved separately from a common malate dehydrogenase ancestor, there are several important struc- tural differences between the two enzymes, notably a five amino acid insertion into the active site loop of P. falciparum LDH.
We find that these active site differences between the two organisms’ LDH likely causes a decrease in the contribution of the previously determined LDH rate promoting vibration to the reaction coordinate of P. falciparum LDH compared to C. parvum LDH, specifically in the coupling of the rate promoting vibration and the hydride transfer.
This effect, while subtle, directly shows how changes in structure near the active site of LDH alter catalytically important motions. Insights provided by studying these alterations would prove useful in determining LDH inhibitors which specifically target the isozymes of these parasitic organisms.
Read full article at: http://pubs.acs.org/doi/abs/10.1021/acs.biochem.7b00245
Related article at: Biochemistry Help Online
Having evolved separately from a common malate dehydrogenase ancestor, there are several important struc- tural differences between the two enzymes, notably a five amino acid insertion into the active site loop of P. falciparum LDH.
We find that these active site differences between the two organisms’ LDH likely causes a decrease in the contribution of the previously determined LDH rate promoting vibration to the reaction coordinate of P. falciparum LDH compared to C. parvum LDH, specifically in the coupling of the rate promoting vibration and the hydride transfer.
This effect, while subtle, directly shows how changes in structure near the active site of LDH alter catalytically important motions. Insights provided by studying these alterations would prove useful in determining LDH inhibitors which specifically target the isozymes of these parasitic organisms.
Read full article at: http://pubs.acs.org/doi/abs/10.1021/acs.biochem.7b00245
Related article at: Biochemistry Help Online
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