4KDE

Crystal Structure of the Apo Form of Thermus thermophilus Malate Dehydrogenase

Summary for 4KDE

• Entry DOI: 10.2210/pdb4kde/pdb
• Descriptor: Malate dehydrogenase (2 entities in total)
• Functional Keywords: dehydrogenase, oxidoreductase
• Biological source: Thermus thermophilus
• Total number of polymer chains: 2
• Total formula weight: 74301.39

Authors

Hsu, C.-H.,Hong, C.-H.,Chang, Y.-Y. (deposition date: 2013-04-25, release date: 2014-02-05, Last modification date: 2024-02-28)

Primary citation

Hung, C.H.,Hwang, T.S.,Chang, Y.Y.,Luo, H.R.,Wu, S.P.,Hsu, C.H.
Crystal structures and molecular dynamics simulations of thermophilic malate dehydrogenase reveal critical loop motion for co-substrate binding.
Plos One, 8:e83091-e83091, 2013

PubMed Abstract: Malate dehydrogenase (MDH) catalyzes the conversion of oxaloacetate and malate by using the NAD/NADH coenzyme system. The system is used as a conjugate for enzyme immunoassays of a wide variety of compounds, such as illegal drugs, drugs used in therapeutic applications and hormones. We elucidated the biochemical and structural features of MDH from Thermus thermophilus (TtMDH) for use in various biotechnological applications. The biochemical characterization of recombinant TtMDH revealed greatly increased activity above 60 °C and specific activity of about 2,600 U/mg with optimal temperature of 90 °C. Analysis of crystal structures of apo and NAD-bound forms of TtMDH revealed a slight movement of the binding loop and few structural elements around the co-substrate binding packet in the presence of NAD. The overall structures did not change much and retained all related positions, which agrees with the CD analyses. Further molecular dynamics (MD) simulation at higher temperatures were used to reconstruct structures from the crystal structure of TtMDH. Interestingly, at the simulated structure of 353 K, a large change occurred around the active site such that with increasing temperature, a mobile loop was closed to co-substrate binding region. From biochemical characterization, structural comparison and MD simulations, the thermal-induced conformational change of the co-substrate binding loop of TtMDH may contribute to the essential movement of the enzyme for admitting NAD and may benefit the enzyme's activity.

PubMed: 24386145
DOI: 10.1371/journal.pone.0083091

Experimental method

X-RAY DIFFRACTION (1.798 Å)