Farnesyltransferase and geranylgeranyltransferase I: structures, mechanism, inhibitors and molecular modeling

Shen, Meifen; Pan, Peichen; Li, Youyong; Li, Dan; Yu, Huidong; Hou, Tingjun

doi:10.1016/j.drudis.2014.10.002

Cited by 41 publications

(36 citation statements)

References 73 publications

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“…It is part of the Ras family of small GTPases, which have been linked to many cellular signaling pathways in cell growth and differentiation, synaptic plasticity, learning, and memory (41)(42)(43). DIRAS1 and DIRAS2 form a biochemically and functionally distinct branch of Ras GTPases, which are characterized by a fast guanidine-nucleotide exchange rate (16).…”

Section: Discussionmentioning

confidence: 99%

Generalized myoclonic epilepsy with photosensitivity in juvenile dogs caused by a defective DIRAS family GTPase 1

Wielaender

Sarviaho

James

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The clinical and electroencephalographic features of a canine generalized myoclonic epilepsy with photosensitivity and onset in young Rhodesian Ridgeback dogs (6 wk to 18 mo) are described. A fully penetrant recessive 4-bp deletion was identified in the DIRAS family GTPase 1 (DIRAS1) gene with an altered expression pattern of DIRAS1 protein in the affected brain. This neuronal DIRAS1 gene with a proposed role in cholinergic transmission provides not only a candidate for human myoclonic epilepsy but also insights into the disease etiology, while establishing a spontaneous model for future intervention studies and functional characterization.seizure | juvenile | canine | photosensitivity | Ras

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Section: Discussionmentioning

confidence: 99%

Generalized myoclonic epilepsy with photosensitivity in juvenile dogs caused by a defective DIRAS family GTPase 1

Wielaender

Sarviaho

James

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…[1][2][3][4][5][6] FTase is a heterodimeric zinc metalloenzyme, responsible for posttranslational modification and activation of Ras proteins. Ras proteins undergo three sequential enzymatic posttranslational modifications.…”

Section: B S T R a C Tmentioning

confidence: 99%

Phenothiazine-based CaaX competitive inhibitors of human farnesyltransferase bearing a cysteine, methionine, serine or valine moiety as a new family of antitumoral compounds

Dumitriu

Bîcu

Belei

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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“…Multiple such compounds have been described, supporting the feasibility of prenylation as a therapeutic target in pathogenic fungi and parasites (Eastman et al , 2006; Hast et al , 2011). Few GGTase inhibitors, however, have been developed or investigated, mostly because of their high toxicity in vivo (Shen et al , 2015b). …”

Section: Overview Of Lipid Modifications Of Proteinmentioning

confidence: 99%

All about that fat: Lipid modification of proteins in Cryptococcus neoformans

Santiago-Tirado

Doering²

2016

J Microbiol.

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Lipid modification of proteins is a widespread, essential process whereby fatty acids, cholesterol, isoprenoids, phospholipids, or glycosylphospholipids are attached to polypeptides. These hydrophobic groups may affect protein structure, function, localization, and/or stability; as a consequence such modifications play critical regulatory roles in cellular systems. Recent advances in chemical biology and proteomics have allowed the profiling of modified proteins, enabling dissection of the functional consequences of lipid addition. The enzymes that mediate lipid modification are specific for both the lipid and protein substrates, and are conserved from fungi to humans. In this article we review these enzymes, their substrates, and the processes involved in eukaryotic lipid modification of proteins. We further focus on its occurrence in the fungal pathogen Cryptococcus neoformans, highlighting unique features that are both relevant for the biology of the organism and potentially important in the search for new therapies.

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Farnesyltransferase and geranylgeranyltransferase I: structures, mechanism, inhibitors and molecular modeling

Cited by 41 publications

References 73 publications

Generalized myoclonic epilepsy with photosensitivity in juvenile dogs caused by a defective DIRAS family GTPase 1

Generalized myoclonic epilepsy with photosensitivity in juvenile dogs caused by a defective DIRAS family GTPase 1

Phenothiazine-based CaaX competitive inhibitors of human farnesyltransferase bearing a cysteine, methionine, serine or valine moiety as a new family of antitumoral compounds

All about that fat: Lipid modification of proteins in Cryptococcus neoformans

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