Dynamic Description of the Catalytic Cycle of Malate Enzyme: Stereoselective Recognition of Substrate, Chemical Reaction, and Ligand Release

Zhang, Pu; Zhao, Mengdi; Zhang, Yue; Sun, Wenhui; Bao, Yongming

doi:10.1021/acs.jpcb.8b05135

Cited by 6 publications

(5 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Stereoselective recognition of molecules is essential for the function of both natural and artificial systems with its kinetic and thermodynamic facets playing important roles . At a fundamental level, the process of chiral recognition rests on the three‐point interaction model in which at least three configurationally dependent noncovalent contacts (or segments in case of axial chirality) are necessary for achieving discrimination of a pair of enantiomers.…”

Section: Introductionmentioning

confidence: 99%

Multivalent C−H⋅⋅⋅Cl/Br−C Interactions Directing the Resolution of Dynamic and Twisted Capsules

Pavlović

Liu

Güney

et al. 2019

Chemistry A European J

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

Multivalent C−H⋅⋅⋅Cl/Br−C Interactions Directing the Resolution of Dynamic and Twisted Capsules

Pavlović

Liu

Güney

et al. 2019

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…Residues involved in catalytic activity (Tyr109, Lys180 and Asp274) and residues known to bind the metal cation cofactor (Glu251, Asp252, Asp275) were strictly conserved in CBU0823, reflecting their crucial functions [37,67,68].…”

Section: Plos Onementioning

confidence: 99%

Characterisation of putative lactate synthetic pathways of Coxiella burnetii

et al. 2021

View full text Add to dashboard Cite

The zoonotic pathogen Coxiella burnetii, the causative agent of the human disease Q fever, is an ever-present danger to global public health. Investigating novel metabolic pathways necessary for C. burnetii to replicate within its unusual intracellular niche may identify new therapeutic targets. Recent studies employing stable isotope labelling established the ability of C. burnetii to synthesize lactate, despite the absence of an annotated synthetic pathway on its genome. A noncanonical lactate synthesis pathway could provide a novel anti-Coxiella target if it is essential for C. burnetii pathogenesis. In this study, two C. burnetii proteins, CBU1241 and CBU0823, were chosen for analysis based on their similarities to known lactate synthesizing enzymes. Recombinant GST-CBU1241, a putative malate dehydrogenase (MDH), did not produce measurable lactate in in vitro lactate dehydrogenase (LDH) activity assays and was confirmed to function as an MDH. Recombinant 6xHis-CBU0823, a putative NAD+-dependent malic enzyme, was shown to have both malic enzyme activity and MDH activity, however, did not produce measurable lactate in either LDH or malolactic enzyme activity assays in vitro. To examine potential lactate production by CBU0823 more directly, [13C]glucose labelling experiments compared label enrichment within metabolic pathways of a cbu0823 transposon mutant and the parent strain. No difference in lactate production was observed, but the loss of CBU0823 significantly reduced 13C-incorporation into glycolytic and TCA cycle intermediates. This disruption to central carbon metabolism did not have any apparent impact on intracellular replication within THP-1 cells. This research provides new information about the mechanism of lactate biosynthesis within C. burnetii, demonstrating that CBU1241 is not multifunctional, at least in vitro, and that CBU0823 also does not synthesize lactate. Although critical for normal central carbon metabolism of C. burnetii, loss of CBU0823 did not significantly impair replication of the bacterium inside cells.

show abstract

“…24 In addition, there is overlap between the MAS and TCA cycle (OAA, oxoglutarate, and malate). 25 Oxoglutarate can also be supplied by other amino acid in TCA cycle. The crucial function of malate is to transfer cytosolic NADH into mitochondria.…”

Section: Mas and The Overlap With Tca Cyclementioning

confidence: 99%

“…55 (3) Another malate-related enzyme is ME, a member of oxidative decarboxylase family catalyzing irreversible oxidative decarboxylation to yield CO 2 and pyruvate, with concomitant reduction of dinucleotide cofactor NAD+ or NADP + . 25,56 And ME2, mitochondrial NAD + dependent, is a mitochondrial enzyme that catalyzes the conversion of malate to pyruvate and CO 2 in the mitochondria of tumor cells while absent in non-tumor tissues. 57 ME2 can directly interact with MAS and generate NADH in mitochondria.…”

Section: Malate and Mdh Indispensable Role In Energy Metabolismmentioning

confidence: 99%

Potential biomarkers in septic shock besides lactate

Yang

Zhang

2020

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

Septic shock can be defined as sepsis with persisting hypotension and is required for vasopressors after initial unsuccessful fluid resuscitation. Elevated lactate is a biomarker of tissue perfusion and oxygenation and a useful prognostic tool for resuscitation in septic shock, as it is a byproduct of anaerobic glycolysis due to inadequate oxygen delivery and tissue hypoxia. Early and serial systematic lactate measurement will prompt physician more rapid intervention and lactate normalization, which is associated with better outcome. However, lactate formation during septic shock is neither entirely related to tissue hypoxia, nor reversible by increasing oxygen delivery. Meanwhile, lactate can be oxidized via tricarboxylic acid cycle after being transferred into mitochondria via lactate shuttle, which indicates elevated lactate can be used rather than only accumulation. Glycolysis and elevated lactate can be initiated by hypoxia, but persistent hyperlactatemia may not only represent persistent hypoxia. Some other potential biomarkers have been reviewed in the article including intermediates of tricarboxylic acid cycle, malate-aspartate shuttle, the nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide (NAD+/NADH) ratio, NAD+, NADH, malate, and malate dehydrogenase from the point of view of energy metabolism. Among them, malate dehydrogenase participates in both malate-aspartate shuttle and tricarboxylic acid cycle, and it can also indirectly reflex the NAD+/NADH ratio. It is reasonable to hypothesize that the combination of lactate and malate dehydrogenase will be more comprehensive to reflex hypoxia in septic shock. Impact statement Elevated lactate has been commonly considered as a biomarker and a useful prognostic tool for resuscitation in septic shock, facilitating physician more rapid intervention and treatment. However, it can be initiated by hypoxia, but persistent hyperlactatemia may not represent persistent hypoxia only. In the article, it is the first time to review potential biomarkers in septic shock from the point of view of energy metabolism including intermediates of TCA cycle, MAS, the NAD+/NADH ratio, NAD+, NADH, malate, and MDH. And the combination of lactate and MDH is also proposed in septic shock for the first time, as MDH in cytoplasm and mitochondria participates in both MAS and TCA cycle for ATP generation. Its feasibility in clinic has been analyzed at the end, although related research is still limited. It is reasonable the combination of lactate and MDH will be more comprehensive to reflex hypoxia in septic shock.

show abstract

Dynamic Description of the Catalytic Cycle of Malate Enzyme: Stereoselective Recognition of Substrate, Chemical Reaction, and Ligand Release

Cited by 6 publications

References 65 publications

Multivalent C−H⋅⋅⋅Cl/Br−C Interactions Directing the Resolution of Dynamic and Twisted Capsules

Multivalent C−H⋅⋅⋅Cl/Br−C Interactions Directing the Resolution of Dynamic and Twisted Capsules

Characterisation of putative lactate synthetic pathways of Coxiella burnetii

Potential biomarkers in septic shock besides lactate

Contact Info

Product

Resources

About