Geranylgeranyl diphosphate synthase: Role in human health, disease and potential therapeutic target

Muehlebach, Molly E; Holstein, Sarah A.

doi:10.1002/ctm2.1167

Cited by 11 publications

(11 citation statements)

References 252 publications

(565 reference statements)

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“…GGPS1 monomers associate into a trimer of dimers, forming a hexamer (Figure 1i). In certain circumstances, an octamer can also form (Kavanagh et al, 2006;Muehlebach & Holstein, 2023). GGPP binds to a mostly hydrophobic GGPS1 pocked formed by residues R28, L31, F35, H57, R73, L122, L155, F156, Al159, V160, and F184 (Consortium PD-K., 2020;Kavanagh et al, 2006) (Figure 1i).…”

Section: Structural Analysis and Predicted Effectmentioning

confidence: 99%

Expanding the phenotypic and genotypic spectrum of GGPS1 related congenital muscular dystrophy

Altassan,

AlQudairy,

AlJebreen

et al. 2023

American J of Med Genetics Pt A

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Congenital muscular dystrophies are a group of progressive disorders with wide range of symptoms associated with diverse cellular mechanisms. Recently, biallelic variants in GGPS1 were linked to a distinct autosomal recessive form of muscular dystrophy associated with hearing loss and ovarian insufficiency. In this report, we present a case of a young patient with a homozygous variant in GGPS1. The patient presented with only proximal muscle weakness, and elevated liver transaminases with spared hearing function. The hepatic involvement in this patient caused by a novel deleterious variant in the gene extends the phenotypic and genotypic spectrum of GGPS1 related muscular dystrophy.

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Section: Structural Analysis and Predicted Effectmentioning

confidence: 99%

Expanding the phenotypic and genotypic spectrum of GGPS1 related congenital muscular dystrophy

Altassan,

AlQudairy,

AlJebreen

et al. 2023

American J of Med Genetics Pt A

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“…GGPPSs also serve as precursors of biosynthesis of a diverse class of specialized terpenoids such as polyterpenes, polyprenols, tocopherols, gibberellins, abscisic acid, strigolactones, phytyl esters, and plastoquinones (Akhtar et al, 2017; Tholl and Lee, 2011). Previously, GGPPSs have been functional characterized in plants, bacteria, yeast and mammals, but the roles of GGPPS in insect species has been scarcely understood so far (Barja & Rodriguez‐Concepcion, 2021; Muehlebach & Holstein, 2023).…”

Section: Introductionmentioning

confidence: 99%

Functional characterization of a geranylgeranyl diphosphate synthase in the leaf beetle Monolepta hieroglyphica

Song,

Liu,

Dhiloo

et al. 2024

Arch Insect Biochem Physiol

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Geranylgeranyl diphosphate synthase (GGPPS) as the short‐chain prenyltransferases for catalyzing the formation of the acyclic precursor (E)‐GGPP has been extensively investigated in mammals, plants, and microbes, but its functional plasticity is poorly understood in insect species. Here, a single GGPPS in leaf beetle Monolepta hieroglyphica, MhieGGPPS, was functionally investigated. Phylogenetic analysis showed that MhieGGPPS was clustered in one clade with homologs and had six conserved motifs. Molecular docking results indicated that binding sites of dimethylallyl diphosphate (DMAPP), (E)‐geranyl pyrophosphate (GPP), and (E)‐farnesyl pyrophosphate (FPP) were in the chain‐length determination region of MhieGGPPS, respectively. In vitro, recombiant MhieGGPPS could catalyze the formation of (E)‐geranylgeraniol against different combinations of substrates including isopentenyl pyrophosphate (IPP)/DMAPP, IPP/(E)‐GPP, and IPP/(E)‐FPP, suggesting that MhieGGPPS could not only use (E)‐FPP but also (E)‐GPP and DMAPP as the allylic cosubstrates. In kinetic analysis, the (E)‐FPP was most tightly bound to MhieGGPPS than that of others. It was proposed that MhieGGPPS as a multifunctional enzyme is differentiated from the other GGPPSs in the animals and plants, which only accepted (E)‐FPP as the allylic cosubstrate. These findings provide valuable insights into understanding the functional plasticity of GGPPS in M. hieroglyphica and the novel biosynthesis mechanism in the isoprenoid pathway.

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“…GGPP serves as a fundamental precursor of various primary and secondary metabolites, including terpenoids, gibberellins, carotenoids, and chlorophyll, in plants. Additionally, GGPP therapies [6,7]. GGPPS genes have been the subject of extensive research in plan have reported that mutations in GGPPS genes can result in seed albinism in Zhou et al (2021) conducted a study in rice and found that the recruitment GGPPS controls the metabolism of chlorophyll biosynthesis [9].…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Identification, Characterization, and Expression Analysis of the Geranylgeranyl Pyrophosphate Synthase (GGPPS) Gene Family Reveals Its Importance in Chloroplasts of Brassica oleracea L.

et al. 2023

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GGPPS (geranylgeranyl pyrophosphate synthase) is a crucial enzyme in the terpene biosynthesis pathway. Terpenoids play essential roles in chlorophyll biosynthesis and the development of cabbage (Brassica oleracea L. var. capitata L.), a major cruciferous vegetable worldwide. However, limited information is available regarding B. oleracea GGPPS genes. In this study, we examined 10 BoGGPPS genes from the B. oleracea genome. The subcellular localization prediction suggests that BoGGPPS proteins are mainly expressed in chloroplasts and plastids. Similar BoGGPPS genes exhibited a similar structure and motif. Distribution, collinearity, and Ka/Ks analysis revealed multiple duplication events within the BoGGPPS gene family. Cabbage BoGGPPS may participate in light and hormone responses via analysis of cis-acting elements. Three-dimensional structure analysis demonstrated the abundance of α-helices and random coils among BoGGPPS members, suggesting their important functions. Based on qRT-PCR, we observed notable differences in the transcript levels of BoGGPPS genes between leaves and siliques. Bol028967 exhibited significantly higher transcript levels in WT (Wild-type) siliques compared to in Boas1 (Brassica oleracea albino silique 1), and subcellular localization analysis confirmed its expression in chloroplasts, implying its essential role in chloroplast synthesis. These findings lay the groundwork for further exploration and in-depth functional analysis of BoGGPPS genes and their relationship with terpenoids in the context of chlorophyll synthesis in B. oleracea.

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Geranylgeranyl diphosphate synthase: Role in human health, disease and potential therapeutic target

Cited by 11 publications

References 252 publications

Expanding the phenotypic and genotypic spectrum of GGPS1 related congenital muscular dystrophy

Expanding the phenotypic and genotypic spectrum of GGPS1 related congenital muscular dystrophy

Functional characterization of a geranylgeranyl diphosphate synthase in the leaf beetle Monolepta hieroglyphica

Genome-Wide Identification, Characterization, and Expression Analysis of the Geranylgeranyl Pyrophosphate Synthase (GGPPS) Gene Family Reveals Its Importance in Chloroplasts of Brassica oleracea L.

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