Structure and catalytic mechanism of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (MECDP) synthase, an enzyme in the non-mevalonate pathway of isoprenoid synthesis.
Precursors for isoprenoid synthesis are essential in all organisms. These compounds are synthesized by one of two known routes: the well characterized mevalonate pathway or a recently discovered non-mevalonate route which is used in many bacteria and human pathogens. Since the second pathway is both vital and unlike any found in humans, enzymes catalysing reactions along this synthetic route are possible drug targets. The structure of one such enzyme from the thermophilic bacterium Thermus thermophilus has been solved to high resolution in the presence of substrate and with a substrate analogue. Enzyme co-crystallized with substrate shows only one product, cytosine monophosphate (CMP), in the active site. At the high resolution of the refinement (1.6 A) the positions and coordination of the magnesium ions in the active site are clearly seen.
Kishida
Hiroyuki
H
Protein Design Laboratory, Graduate School of Integrated Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.
Wada
Takashi
T
Unzai
Satoru
S
Kuzuyama
Tomohisa
T
Takagi
Motoki
M
Terada
Takaho
T
Shirouzu
Mikako
M
Yokoyama
Shigeyuki
S
Tame
Jeremy R H
JR
Park
Sam-Yong
SY
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D003568:Cytidine Monophosphate / Q000378:metabolism; D029968:Escherichia coli Proteins; D008239:Lysine / Q000378:metabolism; D008274:Magnesium / Q000737:chemistry / Q000378:metabolism; D008798:Mevalonic Acid / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019761:Phosphorus-Oxygen Lyases / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011106:Polyisoprenyl Phosphates / Q000096:biosynthesis*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D016963:Thermus thermophilus / Q000201:enzymology
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D011106:Polyisoprenyl Phosphates; D011994:Recombinant Proteins; D019761:Phosphorus-Oxygen Lyases; C400181:ISPF protein, E coli; D003568:Cytidine Monophosphate; D008274:Magnesium; D008239:Lysine; D008798:Mevalonic Acid