7BSL

Crystal Structure of human ME2 R67A mutant

Summary for 7BSL

• Entry DOI: 10.2210/pdb7bsl/pdb
• Descriptor: NAD-dependent malic enzyme, mitochondrial, NICOTINAMIDE-ADENINE-DINUCLEOTIDE (3 entities in total)
• Functional Keywords: malate dehydrogenase, nad-dependent malic enzyme, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 129493.43

Authors

Chen, W.L.,Tai, S.C.,Hung, H.C.,Ho, M.C. (deposition date: 2020-03-30, release date: 2021-02-10, Last modification date: 2023-11-29)

Primary citation

Hsieh, J.Y.,Yang, H.P.,Tewary, S.K.,Cheng, H.C.,Liu, Y.L.,Tai, S.C.,Chen, W.L.,Hsu, C.H.,Huang, T.J.,Chou, C.J.,Huang, Y.N.,Peng, C.T.,Ho, M.C.,Liu, G.Y.,Hung, H.C.
Single nucleotide variants lead to dysregulation of the human mitochondrial NAD(P) + -dependent malic enzyme.
Iscience, 24:102034-102034, 2021

PubMed Abstract: Human mitochondrial NAD(P)-dependent malic enzyme (ME2) is well recognized to associate with cancer cell metabolism, and the single nucleotide variants (SNVs) of ME2 may play a role in enzyme regulation. Here we reported that the SNVs of ME2 occurring in the allosteric sites lead to inactivation or overactivation of ME2. Two ME2-SNVs, ME2_R67Q and ME2-R484W, that demonstrated inactivating or overactivating enzyme activities of ME2, respectively, have different impact toward the cells. The cells with overactivating SNV enzyme, ME2_R484W, grow more rapidly and are more resistant to cellular senescence than the cells with wild-type or inactivating SNV enzyme, ME2_R67Q. Crystal structures of these two ME2-SNVs reveal that ME2_R67Q was an inactivating "dead form," and ME2_R484W was an overactivating "closed form" of the enzyme. The resolved ME2-SNV structures provide a molecular basis to explain the abnormal kinetic properties of these SNV enzymes.

PubMed: 33554057
DOI: 10.1016/j.isci.2021.102034

Experimental method

X-RAY DIFFRACTION (2.55 Å)