4YR9
mouse TDH with NAD+ bound
Summary for 4YR9
| Entry DOI | 10.2210/pdb4yr9/pdb |
| Related | 4YRA 4YRB |
| Descriptor | L-threonine 3-dehydrogenase, mitochondrial, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | l-threonine 3-dehydrogenase, oxidoreductase |
| Biological source | Mus musculus (Mouse) |
| Cellular location | Mitochondrion : Q8K3F7 |
| Total number of polymer chains | 6 |
| Total formula weight | 224666.18 |
| Authors | |
| Primary citation | He, C.,Huang, X.,Liu, Y.,Li, F.,Yang, Y.,Tao, H.,Han, C.,Zhao, C.,Xiao, Y.,Shi, Y. Structural insights on mouse l-threonine dehydrogenase: A regulatory role of Arg180 in catalysis J.Struct.Biol., 192:510-518, 2015 Cited by PubMed Abstract: Mouse L-threonine dehydrogenase (mTDH), which belongs to the short-chain dehydrogenase/reductase (SDR) superfamily and mediates threonine catabolism, plays pivotal roles in both powerful biosynthesis and signaling in mouse stem cells and has a regulatory residue Arg180. Here we determined three crystal structures of mTDH: wild-type (WT) in the apo form; in complex with NAD(+) and a substrate analog, glycerol, or with only NAD(+); as well as the R180K variant with NAD(+). This is the first description of a structure for mammalian SDR-type TDH. Structural comparison revealed the structural basis for SDR-type TDH catalysis remains strictly conserved in bacteria and mammals. Kinetic enzyme assays, and isothermal titration calorimetry (ITC) measurements indicated the R180K mutation has little effect on NAD(+) binding affinity, whereas affects the substrate's affinity for the enzyme. The crystal structure of R180K with NAD(+), biochemical and spectroscopic studies suggested that the R180K mutant should bind NAD(+) in a similar way and have a similar folding to the WT. However, the R180K variant may have difficulty adopting the closed form due to reduced interaction of residue 180 with a loop which connects a key position for mTDH switching between the closed and open forms in mTDH catalysis, and thereby exhibited a significantly decreased kcat/Km value toward the substrate, L-Thr. In sum, our results suggest that activity of GalE-like TDH can be regulated by remote interaction, such as hydrogen bonding and hydrophobic interaction around the Arg180 of mTDH. PubMed: 26492815DOI: 10.1016/j.jsb.2015.10.014 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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