5J32: Isopropylmalate Dehydrogenase In Complex With Isopropylmalate

Isopropylmalate dehydrogenase (IPMDH) and 3-(2'-methylthio)ethylmalate dehydrogenase catalyze the oxidative decarboxylation of different beta-hydroxyacids in the leucine- and methionine-derived glucosinolate biosynthesis pathways, respectively, in plants. Evolution of the glucosinolate biosynthetic enzyme from IPMDH results from a single amino acid substitution that alters substrate specificity. Here, we present the x-ray crystal structures of Arabidopsis thaliana IPMDH2 (AtIPMDH2) in complex with either isopropylmalate and Mg(2+) or NAD(+) These structures reveal conformational changes that occur upon ligand binding and provide insight on the active site of the enzyme. The x-ray structures and kinetic analysis of site-directed mutants are consistent with a chemical mechanism in which Lys-232 activates a water molecule for catalysis. Structural analysis of the AtIPMDH2 K232M mutant and isothermal titration calorimetry supports a key role of Lys-232 in the reaction mechanism. This study suggests that IPMDH-like enzymes in both leucine and glucosinolate biosynthesis pathways use a common mechanism and that members of the beta-hydroxyacid reductive decarboxylase family employ different active site features for similar reactions.
PDB ID: 5J32Download
MMDB ID: 139203
PDB Deposition Date: 2016/3/30
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 1.93  Å
Source Organism:
Similar Structures:
Biological Unit for 5J32: dimeric; determined by author and by software (PISA)
Molecular Components in 5J32
Label Count Molecule
Proteins (2 molecules)
3-isopropylmalate Dehydrogenase 2, Chloroplastic(Gene symbol: IMD2)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB