Function
4-hydroxy-2-methylbut-2-enyl diphosphate reductase (also known as IspH or LytB reductase) is an containing protein. IspH converts 1-hydroxy-2-methylbut-2-enyl 4-diphosphate into isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). IspH participates in isoprenoid biosynthesis. IspH is the last enzyme in the nonmevalonate pathway. [1]
It is an enzyme involved in the biosynthesis of isoprenoids, a diverse class of natural products that play critical roles in various cellular processes. Isoprenoids have essential functions as components of lipids, pigments, hormones, and signaling molecules in all organisms.
IspH catalyzes a crucial step in the non-mevalonate pathway (also known as the MEP pathway or DOXP/MEP pathway), which is an alternative pathway for the biosynthesis of isoprenoids in many bacteria, algae, and plant plastids. This pathway is distinct from the mevalonate pathway found in animals.
Specifically, IspH converts 4-hydroxy-3-methylbut-2-enyl diphosphate (HMBPP) into isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). IPP and DMAPP are the central building blocks for the synthesis of longer-chain isoprenoids such as carotenoids, chlorophylls, and quinones.
The reaction catalyzed by IspH involves the reduction of HMBPP, an unsaturated diphosphate compound, to form IPP and DMAPP, which are saturated isoprenoid precursors. This reduction is dependent on an iron-sulfur cluster cofactor and NAD(P)H as a source of reducing equivalents.
The activity of IspH is critical for maintaining the proper balance of IPP and DMAPP, which are required for the synthesis of a wide variety of essential isoprenoids. Dysregulation or inhibition of IspH can disrupt isoprenoid biosynthesis and have significant effects on cellular functions.
Given its essential role in isoprenoid biosynthesis, IspH has attracted attention as a potential target for the development of antimicrobial and herbicidal agents. Inhibition of IspH activity could selectively disrupt isoprenoid metabolism in pathogens or weeds, providing a strategy for the development of new drugs or herbicides with reduced side effects on the host organism.
In summary, 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (IspH) is an enzyme involved in the non-mevalonate pathway of isoprenoid biosynthesis. It catalyzes the conversion of 4-hydroxy-3-methylbut-2-enyl diphosphate (HMBPP) to isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), which are important building blocks for the synthesis of diverse isoprenoid compounds.
Disease
IspH is involved in penicillin tolerance.
Structural highlights
- is shown.
- .
- Of note, .
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- . Water molecules are shown as red spheres.
- (PDB code 3szl).[2]
3D structures of 4-hydroxy-3-methylbut-2-enyl diphosphate reductase
4-hydroxy-3-methylbut-2-enyl diphosphate reductase 3D structures
