EC Number   |
General Information |
Reference |
|---|
    2.7.7.60 | evolution |
structure, function and mechanism of Plasmodium IspD homologs from their evolutionary imprints, e.g. Theileria annulata. Structure-based phylogeny for PlIspD homologues, constructed by using the maximum likelihood algorithm with the Dayhoff model structure and structure motifs prediction and characterization of PlIspD homologues, overview |
-, 761602 |
| 2.7.7.60 | evolution |
the enzyme is a member of the cytidylyltransferase family of enzymes that utilize cytidine 5'-triphosphate (CTP) to synthesize molecules that are typically precursors to membrane phospholipids |
737438 |
| 2.7.7.60 | malfunction |
the inhibition of DXR (EC 1.1.1.267, MEP synthase) dramatically reduces IspD function in cells. Phosphonic acid antibiotic fosmidomycin is a substrate mimic and inhibitor of DXR. The inhibition of downstream enzyme IspD is also metabolically apparent in fosmidomycin-treated cells, although IspD homologues are not directly inhibited by fosmidomycin in vitro |
-, 760261 |
| 2.7.7.60 | malfunction |
the inhibition of DXR (EC 1.1.1.267, MEP synthase) dramatically reduces IspD function in cells. Phosphonic acid antibiotic fosmidomycin is a substrate mimic and inhibitor of DXR.13 The inhibition of downstream enzyme IspD is also metabolically apparent in fosmidomycin-treated cells, although IspD homologues are not directly inhibited by fosmidomycin in vitro. 1R,3S-MMV008138-treated parasites supplemented with 0.2 mM isopentenyl diphosphate (IPP) are viable, but 1R,3S-MMV008138 treatment of such IPP-rescued cells still results in a significant reduction in methylerythritol cyclic diphosphate (MEcPP) levels, the most distal MEP metabolite detected |
760261 |
| 2.7.7.60 | metabolism |
the MEP cytidylyltransferase, or IspD catalyzes the second committed step of the methyl erythritol phosphate (MEP) pathway. The MEP pathway is essential for the production of isoprenoids |
-, 760333 |
| 2.7.7.60 | more |
molecular dynamics simulation, homology PvIspD structure prediction by comparative modeling technique using the Escherichia coli IspD crystal structure (PDB ID 1I52) as template, and three-dimensional modeling of PvIspD. The conserved domain (NCBI) analysis of translated sequences (619 a.a.) shows the presence of Glycosyl transferase family A (GT-A) domain spanning the amino acid residues 191-558. The two signature motifs of the IspD proteins in this domain viz. GXG and [IVT]-[LIVMC]-[IVT]-[HS]-D-[SGAV]-[AV]-R are also observed in PVX_081425 and all Indian PvIspD sequences by PROSITE as 199GXG201 and 424ILVHDGAR431. Key residues R431 and K548 form the salt bridge with CTP |
-, 761199 |
| 2.7.7.60 | more |
the concerted movements of the P-loop and loops close to the active site are essential in the reaction catalyzed by IspD. The intact P-loop is observed in the apo structure of IspD enzyme. The P-loop comprising residues 8-21 in the apo form I are refined satisfactorily, the B-factor of 30 A2 is almost the same as the average B-factor of all the protein atoms, this loop is highly conserved in the IspD enzymes. BsIspD structure, overview. The active site of BsIspD is covered by P-loop; hydrogen bonding interactions are formed between P-loop and adjacent residues. Upon CTP binding, conformational changes are observed on P-loop, L1-loop and L2-loop. The N-terminal half of the P-loop flips upward from active pocket and the C-terminal half flips down right, the active pocket is open to accommodate the CTP. A cleft is formed between L1-loop and P-loop, favoring for the binding of the cytosine base of CTP, at the same time, the residue Arg15 in the P-loop forms hydrogen bond to the residue Thr211 in L2-loop |
-, 762421 |
| 2.7.7.60 | more |
the enzyme's catalytic pocket, which actively participates in interaction with ligands, mainly consists of polar amino acid residues, three-dimensional modeling of the IspD protein |
-, 761358 |
| 2.7.7.60 | more |
the Pf ISPD genetic locus is refractory to disruption in malaria parasites, providing independent genetic validation for efforts targeting this enzyme |
760261 |
| 2.7.7.60 | physiological function |
2-C-methyl-D-erythritol 4-phosphate cytidyltransferase (IspD) is an essential enzyme in the mevalonate-independent pathway of isoprenoid biosynthesis. This enzyme catalyzes 2-C-methyl-derythritol 4-phosphate (MEP) and cytosine triphosphate (CTP) to 4-diphosphocytidyl-2-C-methyl-derythritol (CDPME) and diphosphate |
-, 762421 |
