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PDBsum entry 1u3p
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structure of 2c-Methyl-D-Erythritol-2,4-Cyclodiphosphate synthase involved in mevalonate-Independent biosynthesis of isoprenoids.
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Authors
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S.Steinbacher,
J.Kaiser,
J.Wungsintaweekul,
S.Hecht,
W.Eisenreich,
S.Gerhardt,
A.Bacher,
F.Rohdich.
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Ref.
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J Mol Biol, 2002,
316,
79-88.
[DOI no: ]
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PubMed id
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Abstract
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Isoprenoids are biosynthesized from isopentenyl diphosphate and the isomeric
dimethylallyl diphosphate via the mevalonate pathway or a mevalonate-independent
pathway that was identified during the last decade. The non-mevalonate pathway
is present in many bacteria, some algae and in certain protozoa such as the
malaria parasite Plasmodium falciparum and in the plastids of higher plants, but
not in mammals and archaea. Therefore, these enzymes have been recognised as
promising drug targets. We report the crystal structure of Escherichia coli 2C-
methyl-d-erythritol-2,4-cyclodiphosphate synthase (IspF), which converts
4-diphosphocytidyl-2C-methyl-d-erythritol 2-phosphate into
2C-methyl-d-erythritol 2,4-cyclodiphosphate and CMP in a Mg-dependent reaction.
The protein forms homotrimers that tightly bind one zinc ion per subunit at the
active site, which helps to position the substrate for direct attack of the
2-phosphate group on the beta-phosphate.
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Figure 1.
Figure 1. Non-mevalonate pathway of isopentenyl and
dimethylallyldiphosphate biosynthesis. (a) Pyruvate and
glyceraldehyde 3-phosphate are condensed to (b) 1-deoxy- Image
-xylulose 5-phosphate, which is converted into (c) 2C-methyl-
Image -erythritol 4-phosphate. Condensation with CTP yields (d)
4-diphosphocytidyl-2C-methyl- Image -erythritol, which is
converted into (d) 4-diphosphocytidyl-2C-methyl- Image
-erythritol 2-phosphate. The last step identified so far is the
cyclisation of the latter to (f) 2C-methyl- Image -erythritol
2,4-cyclodiphosphate by IspF.
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Figure 4.
Figure 4. Omit electron density for bound substrate and
product molecules contoured at 2.5s (stereo view). All complexes
were prepared by soaking. (a) Product complex with bound CMP and
2C-methyl- Image -erythritol 2,4-cyclodiphosphate (data set
Prod). (b) Substrate complex with bound
4-diphosphocytidyl-2C-methyl- Image -erythritol 2-phosphate and
zinc removed with EDTA; the green ball represents the zinc
position in the active enzyme (data set CDP-MEP). (c) Complex
with 4-diphosphocytidyl-2C-methyl- Image -erythritol (data set
CDP-ME). (d) Complex with MgCDP; the Mg ion bridges the a and
b-phosphate groups of CDP (data set MgCDP).
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2002,
316,
79-88)
copyright 2002.
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