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3-D STRUCTURES with LIGANDS
There are 5 categories of structures with ligands.
Category 1
Structures showing Ligands using multi-compound libraries, "fragment cocktails"
Cocktail #2:
4-amino-2-methylquinoline
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Lmaj004144AAA
Fit of chemical fragment to observed difference density in L Major adenylate kinase after soaking in cocktail #2. The observed density is consistent only with 4-amino-2-methylquinoline (lower right in panel of cocktail constituents).
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Cocktail #68:
5-phenyl-2-furoic acid
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Pfal005984AAA
Fit of chemical fragment to observed 3σ difference density in the active site of P falciparum phosphoglycerate mutase after soaking in cocktail #68. The observed density is consistent only with 5-phenyl-2-furoic acid (lower right in panel of cocktail constituents).
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Tbru015777AAA
Crystals of Nucleoside 2-deoxyribosyltransferase (2A0K) were soaked for 12-24 hours with unspecific ligand soaks e.g. Cocktail#4 in order to discover compounds which bind in the groove of the active site for future drug development. Three out of eight data sets with different ligand cocktails resulted in additional identifiable electron density in the groove as shown in two orientations with their corresponding 1.5 σ electron density maps. The identified compound is highlighted in red in the schematic drawing of all compounds present in Cocktail #4.
[ PDB-ID 2A0K ]
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Cocktail #4:
1,2-DIHYDROBENZO[CD]INDOL-2-ONE
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| - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - |
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Cocktail #5:
6-AMINO-1-NAPHTHOL
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| - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - |
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Cocktail #68:
2-(2,5-DIMETHYL-1,3-THIAZOL-4-YL)ACETIC ACID
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Category 2
Structures with added metabolite Ligands
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Tbru015978AAA
Left: density for the orotate bound to Tbru015978AAA (dihydro orotate dehydrogenase). Right: the orotate and FMN bound to Tbru015978AAA.
[ PDB-ID 2B4G ]
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Category 3
Structures with inhibitor Ligands
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Tcru0013382AAA
Bound to cyclosporin
Cyclophilin (Cyclosporin-A binding protein) Potential drug target PDB 1XQ7 Cyclophilin complexed with known anti-Leishmanial agent Cyclosporin
[ PDB-ID 1XQ7 ]
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Category 4
Structures with metabolite Ligands from E. coli
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Tbru015978AAA
Left: density for the FMN bound to Tbru015978AAA (dihydro orotate dehydrogenase). Right: the orotate and FMN bound to Tbru015978AAA.
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Pfal004546AAA (1Y13)
Plasmodium falciparum 6-pyruvoyl tetrahydrobiopterin synthase (PTPS) The blue electrondensity map surrounding biopterin is contoured at 1.5 sigma levels, in magenta the 5 sigma anomalous difference map of a nearby zinc ion is clearly visible. Biopterin is bound in the active site of the protein between two neighboring subunits
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Lmaj004144AAA
The L. major gene encoding a kinase with distant sequence homology to the nuclear AK6 was solved to 1.7 Å resolution The electron density of all datasets from this target shows a high-occupancy Mn ADP as shown. No ADP or ATP was added to any of the solutions used during purification, crystallization, metal/halide soaking, or cryoprotection.
[ PDB-ID 1Y63 ]
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Pfal007254AAA
Plasmodium falciparum D-glyceraldehyde-3-phosphate dehydrogenase
The cofactor NAD is shown as a ball-and-stick model, which was bound to all four subunits of the tetrameric enzyme displaying excellent electron densities.
[ PDB-ID 1ZYA ]
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Lmaj004091AAA
Lmaj004091AAA is the first member of Pfam family 05891/DUF858 deposited in the PDB (1XTP). It appears to be a methyl-transferase for an unknown substrate. We could identify Se-adenosyl-selenohomocysteine as cofactor due to large anomalous differences at the expected sulfur site.
[ PDB-ID 1XTP ]
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Category 5
Structures with surprise Ligands
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Pfal007254AAA
Here is a detailed view from the active site region of SGPP target Pfal007254AAA, Plasmodium falciparum Glyceraldehyde-3-phosphate dehydrogenase. A molecule of AEBSF, which is a protease inhibitor used during purification of the protein, is found bound near the active site. The first image shows the electron density in the region with AEBSF shown in the middle of the scene. The second image shows the AEBSF and its electron density from two different viewpoints, separated by 90 degrees.
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