Farnesyl Diphosphate Synthase. Altering the Catalytic Site To Select for Geranyl Diphosphate Activity†

Biochemistry ◽  
2000 ◽  
Vol 39 (50) ◽  
pp. 15316-15321 ◽  
Author(s):  
Suzanne M. Stanley Fernandez ◽  
Brenda A. Kellogg ◽  
C. Dale Poulter
Keyword(s):  
Catalytic Site ◽  
Farnesyl Diphosphate ◽  
Farnesyl Diphosphate Synthase ◽  
Geranyl Diphosphate

Farnesyl Diphosphate Synthase Reactions of Geranyl Diphosphate Analogues Having Oxygen Atoms in Their Alkyl Chains

1994 ◽  
Vol 23 (10) ◽  
pp. 1841-1844 ◽  
Author(s):  
Yuji Maki ◽  
Hikaru Satoh ◽  
Masayo Kurihara ◽  
Takae Endo ◽  
Gotaro Watanabe ◽  
...  
Keyword(s):  
Farnesyl Diphosphate ◽  
Farnesyl Diphosphate Synthase ◽  
Geranyl Diphosphate ◽  
Alkyl Chains ◽  
Oxygen Atoms

scholarly journals Purification, Enzymatic Characterization, and Inhibition of theZ-Farnesyl Diphosphate Synthase fromMycobacterium tuberculosis

2001 ◽  
Vol 276 (15) ◽  
pp. 11624-11630 ◽  
Author(s):  
Mark C. Schulbach ◽  
Sebabrata Mahapatra ◽  
Marco Macchia ◽  
Silvia Barontini ◽  
Chiara Papi ◽  
...  
Keyword(s):  
Expression System ◽  
Farnesyl Diphosphate ◽  
Farnesyl Diphosphate Synthase ◽  
Isopentenyl Diphosphate ◽  
Enzymatic Characterization ◽  
Geranyl Diphosphate ◽  
Reading Frame ◽  
Absolute Requirement ◽  
Ph Range ◽  
Mycobacterial Cell Wall

We have recently shown that open reading frame Rv1086 of theMycobacterium tuberculosisH37Rv genome sequence encodes a unique isoprenyl diphosphate synthase. The product of this enzyme,ω,E,Z-farnesyl diphosphate, is an intermediate for the synthesis of decaprenyl phosphate, which has a central role in the biosynthesis of most features of the mycobacterial cell wall, including peptidoglycan, arabinan, linker unit galactan, and lipoarabinomannan. We have now purifiedZ-farnesyl diphosphate synthase to near homogeneity using a novel mycobacterial expression system.Z-Farnesyl diphosphate synthase catalyzed the addition of isopentenyl diphosphate toω,E-geranyl diphosphate orω,Z-neryl diphosphate yieldingω,E,Z-farnesyl diphosphate andω,Z,Z-farnesyl diphosphate, respectively. The enzyme has an absolute requirement for a divalent cation, an optimal pH range of 7–8, andKmvalues of 124 μmfor isopentenyl diphosphate, 38 μmfor geranyl diphosphate, and 16 μmfor neryl diphosphate. Inhibitors of theZ-farnesyl diphosphate synthase were designed and chemically synthesized as stable analogs ofω,E-geranyl diphosphate in which the labile diphosphate moiety was replaced with stable moieties. Studies with these compounds revealed that the active site ofZ-farnesyl diphosphate synthase differs substantially fromE-farnesyl diphosphate synthase from pig brain (Sus scrofa).

scholarly journals Inhibitors of Leishmania Major Farnesyl Diphosphate Synthase: Crystallographic and Calorimetric Studies

2011 ◽  
Vol 100 (3) ◽  
pp. 218a-219a
Author(s):  
Srinivas Aripirala ◽  
Sandra Gabelli ◽  
Eric Oldfield ◽  
Dolores Gonzalez Pacanowska ◽  
Mario Amzel
Keyword(s):  
Leishmania Major ◽  
Farnesyl Diphosphate ◽  
Farnesyl Diphosphate Synthase ◽  
Calorimetric Studies

scholarly journals Farnesyl Diphosphate Synthase Inhibitors from In Silico Screening

2013 ◽  
Vol 81 (6) ◽  
pp. 742-748 ◽  
Author(s):  
Steffen Lindert ◽  
Wei Zhu ◽  
Yi‐Liang Liu ◽  
Ran Pang ◽  
Eric Oldfield ◽  
...  
Keyword(s):  
In Silico ◽  
Farnesyl Diphosphate ◽  
Farnesyl Diphosphate Synthase ◽  
In Silico Screening
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