Target intelligence / Profile preview

Dihydrolipoamide dehydrogenase (P64k) (P64k)

Target
P64k
Molecular classification
Enzyme, Oxidoreductase, Flavoenzyme, Carrier protein
01

Overview

P64k is a 64 kDa dihydrolipoamide dehydrogenase (LpdA) derived from Neisseria meningitidis, where it serves as the E3 component of the pyruvate dehydrogenase multienzyme complex (1.2.2, 1.2.4). It plays a critical role in bacterial energy metabolism by catalyzing the NAD+-dependent oxidation of dihydrolipoamide to lipoamide (1.2.1). Beyond its metabolic function, P64k is highly immunogenic and is widely utilized as a carrier protein in therapeutic vaccines to enhance the immune response against weak antigens (1.3.1, 1.3.2). Its most prominent application is in CIMAvax-EGF, a therapeutic vaccine for non-small cell lung cancer (NSCLC), where it is conjugated to human epidermal growth factor (EGF) (1.5.1, 1.5.5). In this context, P64k acts to break the immune system's tolerance to self-EGF, inducing the production of neutralizing antibodies that sequester circulating EGF and deprive tumors of essential growth signals (1.5.4, 1.5.5).

Other names
LpdAE3 componentNeisserial P64k antigenProtein P64kDihydrolipoyl dehydrogenase
02

Mechanism of action

Acts as an immunological carrier protein that enhances the immune response against conjugated weak antigens, such as epidermal growth factor (EGF), by breaking self-tolerance and recruiting T-cell help.

03

Biological functions

Pyruvate metabolismRedox homeostasisEnergy productionGlycine cleavage
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Disease associations

InfectionCancerMeningococcal diseaseNon-small cell lung cancer
05

Safety considerations

Injection site reactionsFeverChillsHeadache
06

Interacting drugs

CIMAvax-EGF
07

Biomarkers

Serum EGF levelsAnti-EGF antibody titersAnti-P64k antibody titers

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