Structure of the GcpE (IspG)–MEcPP complex from Thermus thermophilus

摘要

Isoprenoidprecursorbiosynthesisoccursthroughthemevalonateorthemethylerythritolphosphate(MEP)pathway,usedi.e.,byhumansandbymanyhumanpathogens,respectively.IntheMEPpathway,2‐C‐methyl‐d‐erythritol‐2,4‐cyclo‐diphosphate(MEcPP)isconvertedto(E)‐1‐hydroxy‐2‐methyl‐but‐2‐enyl‐4‐diphosphate(HMBPP)bytheiron–sulfurclusterenzymeHMBPPsynthase(GcpE).ThepresentedX‐raystructureoftheGcpE–MEcPPcomplexfromThermusthermophilusat1.55?resolutionprovidesvaluableinformationaboutthecatalyticmechanismandforrationalinhibitordesign.MEcPPbindinginsidetheTIM‐barrelfunnelinducesa60°rotationofthe[4Fe–4S]clustercontainingdomainontotheTIM‐barrelentrance.Theapicalironofthe[4Fe–4S]clusterligateswiththeC3oxygenatomofMEcPP...