Disease relevance of HEM14

• Both mutations introduced independently in the wild-type HEM14 gene completely inactivated the protein when analyzed in an Escherichia coli expression system [1].
• Yeast protoporphyrinogen oxidase was somewhat similar to the HemY gene product of Bacillus subtilis and to the human and mouse protoporphyrinogen oxidases [1].
• By analogy to human porphyria, the accumulation could be attributed to decreased (Mg or Fe)-chelatase or protoporphyrinogen oxidase activities [2].

High impact information on HEM14

• In this paper, we investigate the functional role for the palmitoylation of an atypical membrane-bound protein, yeast protoporphyrinogen oxidase, which is the molecular target of diphenyl ether-type herbicides [3].
• Acylation stabilizes a protease-resistant conformation of protoporphyrinogen oxidase, the molecular target of diphenyl ether-type herbicides [3].
• Palmitoylation of protoporphyrinogen oxidase has been demonstrated to occur in vivo both in yeast cells and in a heterologous bacterial expression system, where it may be inhibited by cerulenin leading to the accumulation of degradation products of the protein [3].
• We suggest that the active site of protoporphyrinogen oxidase is in the C-terminal domain of the protein, at the interface between the C- and N-terminal domains [4].
• The mixed inhibition by acifluorfen-methyl previously reported for the membrane-bound protoporphyrinogen oxidase (Camadro, J.M., Matringe, M., Scalla, R., and Labbe, P. (1991) Biochem. J. 277, 17-21) was shown to be related to partial proteolysis of the enzyme [5].

Biological context of HEM14

• The phenotype of the null mutant together with the homology of YER014p to human protoporphyrinogen oxidase provide compelling evidence that YER014 is HEM14 [6].
• Kinetics of protoporphyrinogen oxidase inhibition by diphenyleneiodonium derivatives [7].
• Acifluorfen-methyl was strongly inhibitory to protoporphyrinogen oxidase activities whatever their origins [concn. causing 50% inhibition (IC50) = 4 nM for the corn etioplast enzyme] [2].
• This reading frame codes for a protein homologous to human protoporphyrinogen oxidase [6].
• We have used an antisense expression technology in Arabidopsis based on the yeast GAL4/UAS transactivation system (Guyer et al., Genetics, 1998; 149:633-639) to reduce levels of protoporphyrinogen IX oxidase (PPO), the last common enzyme of the biosynthesis of the haem group and chlorophyll [8].

Anatomical context of HEM14

• This photolabeled polypeptide was not detected in a protoporphyrinogen-oxidase-deficient yeast strain, but the membranes contained an equivalent amount of inactive immunoreactive protoporphyrinogen oxidase protein [9].
• The enzyme, protoporphyrinogen oxidase, associated with purified mitochondria isolated from Saccharomyces cerevisiae was solubilized by sonic treatment in the presence of detergent and partially purified [10].

Associations of HEM14 with chemical compounds

• Protoporphyrinogen oxidase, which catalyzes the oxygen-dependent aromatization of protoporphyrinogen IX to protoporphyrin IX, is the molecular target of diphenyl ether type herbicides [1].
• Protoporphyrinogen oxidase inhibition by three peroxidizing herbicides: oxadiazon, LS 82-556 and M&B 39279 [11].
• The diazoketone derivative of tritiated acifluorfen was used to specifically photolabel yeast protoporphyrinogen oxidase [9].
• Inhibition of mitochondrial protein synthesis in regenerating rat livers by thiamphenicol led, instead, to a slight increase in protoporphyrinogen oxidase activity [12].
• It is concluded that, in yeast, the inhibitory effect of anaerobiosis on heme synthesis is due, at least in part, to the requirement for oxygen in the oxidation of protoporphyrinogen IX, and that the effect of glucose on heme biosynthesis is mediated via glucose repression of protoporphyrinogen oxidase and possibly ferrochelatase [13].

Analytical, diagnostic and therapeutic context of HEM14

• Structural features of yeast protoporphyrinogen oxidase were assessed by circular dichroism studies on the enzyme purified from E. coli cells engineered to overproduce the protein [14].

References