MSGPP | Structures Solved with Ligands

		Pfal009167AAA Plasmodium falciparum Putative D-Ribulose 5-Phosphate 3-Epimerase Showing density compatible with 3-aminopyrrolidine from cocktail #68

	5-phenyl-2-furoic acid	Pfal005984AAA Plasmodium falciparum Phosphoglycerate mutase Observed difference density in the active site of phosphoglycerate mutase after soaking in cocktail #68. The observed density is consistent only with 5-phenyl-2-furoic acid

		Tbru015777AAA Trypanosoma brucei Nucleoside 2-deoxyribosyltransferase The ligand bound in the active site is BENZO[CD]INDOL-2-ONE [ PDB-ID 2F67 ] Bosch J, Robien MA, Mehlin C, Boni E, Riechers A, Buckner FS, Van Voorhis WC, Myler PJ, Worthey EA, DeTitta G, Luft JR, Lauricella A, Gulde S, Anderson LA, Kalyuzhniy O, Neely HM, Ross J, Earnest TN, Soltis M, Schoenfeld L, Zucker F, Merritt EA, Fan E, Verlinde CL, Hol W.G. J. Med. Chem. (2006) 49: 5939-5946
		Tbru015777AAA Trypanosoma brucei Nucleoside 2-deoxyribosyltransferase The ligand bound in the active site is (2-ETHYLPHENYL)METHANOL [ PDB-ID 2F62 ] Bosch J, Robien MA, Mehlin C, Boni E, Riechers A, Buckner FS, Van Voorhis WC, Myler PJ, Worthey EA, DeTitta G, Luft JR, Lauricella A, Gulde S, Anderson LA, Kalyuzhniy O, Neely HM, Ross J, Earnest TN, Soltis M, Schoenfeld L, Zucker F, Merritt EA, Fan E, Verlinde CL, Hol W.G. J. Med. Chem. (2006) 49: 5939-5946
		Tbru015777AAA Trypanosoma brucei Nucleoside 2-deoxyribosyltransferase The ligand bound in the active site is 1-METHYLQUINOLIN-2(1H)-ONE [ PDB-ID 2F64 ] Bosch J, Robien MA, Mehlin C, Boni E, Riechers A, Buckner FS, Van Voorhis WC, Myler PJ, Worthey EA, DeTitta G, Luft JR, Lauricella A, Gulde S, Anderson LA, Kalyuzhniy O, Neely HM, Ross J, Earnest TN, Soltis M, Schoenfeld L, Zucker F, Merritt EA, Fan E, Verlinde CL, Hol W.G. J. Med. Chem. (2006) 49: 5939-5946
		Tbru015777AAA Trypanosoma brucei Nucleoside 2-deoxyribosyltransferase The ligand bound in the active site is 5-AMINOISOQUINOLINE [ PDB-ID 2F2T ] Bosch J, Robien MA, Mehlin C, Boni E, Riechers A, Buckner FS, Van Voorhis WC, Myler PJ, Worthey EA, DeTitta G, Luft JR, Lauricella A, Gulde S, Anderson LA, Kalyuzhniy O, Neely HM, Ross J, Earnest TN, Soltis M, Schoenfeld L, Zucker F, Merritt EA, Fan E, Verlinde CL, Hol W.G. J. Med. Chem. (2006) 49: 5939-5946

		Lmaj006828AAA Leishmania major Coproporphyrinogen 3 Oxidase With cyclopentyl acetic acid from cocktail #61
		Lmaj006828AAA Leishmania major Coproporphyrinogen 3 Oxidase With 5-fluoroindole-2-carboxylic acid from cocktail #68

	4-amino-2-methylquinoline	Lmaj004144AAA Leishmania major Adenylate kinase Observed difference density after soaking in cocktail #2. The observed density is consistent only with 4-amino-2-methylquinoline

		Lnai002302AAC Leishmania naiffi Uracil-DNA glycosylase With 4-morpholinopyridine from cocktail #38 and DMSO
		Lnai002302AAC Leishmania naiffi Uracil-DNA glycosylase With 5-chloro-2-methoxybenzoic acid from cocktail #30 and DMSO
		Lnai002302AAC Leishmania naiffi Uracil-DNA glycosylase With 8-hydroxyquinoline-2-carboxylic acid from cocktail #5, DMSO, and glycerol
		Lnai002302AAC Leishmania naiffi Uracil-DNA glycosylase With 1H-imidazole-4-carbothioamide from from cocktail #64

Category 2
Structures with synthetic inhibitors


		Pviv005676AAA Plasmodium vivax Adenosine deaminase With pentostatin bound. Left: sigmaA-weighted ligand-omit difference map of pentostatin (2'Deoxycoformycin, DCF) (3.5 σ). Right: ligand as sticks and protein as ribbons. [ PDB-ID 2PGR ]

		Tcru0013382AAA Trypanosoma cruzi Cyclophilin (Cyclosporin-A binding protein) Potential drug target Cyclophilin PDB 1XO7 complexed with known anti-Leishmanial agent Cyclosporin [ PDB-ID 1XQ7 ]

		Lnai002302AAC Leishmania naiffi Uracil-DNA glycosylase With 5-bromouracil, a metabolite analog [ PDB-ID 3CXM ]

Category 3
Structures with added metabolite Ligands

		Pfal008421AAA Plasmodium falciparum Purine nucleoside phosphorylase (PNP) With inosine bound [ PDB-ID 2BSX ]

		Pviv008894AAA Plasmodium vivax Guanylate kinase With guanosine-5'-monophosphate and pyrophosphate bound. Left: density of ligands and protein. Right: ligands as sticks, protein as ribbons. [ PDB-ID 2QOR ]

		Pviv005676AAA Plasmodium vivax Adenosine deaminase With adenosine bound. Left: SigmaA-weighted ligan-omit difference map of adenosine (4 σ). Right: Ligand as sticks and protein as ribbons. [ PDB-ID 2PGF ]
		Pviv005676AAA Plasmodium vivax Adenosine deaminase With guanosine bound: SigmaA-weighted ligand-omit difference map (4 σ). [ PDB-ID 2QVN ]

		Tbru022584AAA Trypanosoma brucei Seryl-tRNA synthetase Seryladenylate in active site after soaking with serine and ATP

		Tbru015978AAA Trypanosoma brucei Dihydroorotate dehydrogenase Left: density for orotate bound to Tbru015978AAA. Right: the orotate and FMN bound to Tbru015978AAA. [ PDB-ID 2B4G ]

		Tbru017883AAA Trypanosoma brucei Uridine Phosphorylase With uracil (showing) and ribose-1-phosphate (mostly hidden) bound.. [ PDB-ID 3BJE ]

		Tcru019078AAA Trypanosoma cruzi Spermidine synthase With S-Adenosyl Methionine bound, F_o - F_c map. [ PDB-ID 3BWC ]

		Tcru008378AAB Trypanosoma cruzi histidyl-tRNA synthetase With L-histidyl-adenosyl-monophosphate from co-crystallization with His then soaking with ATP and Mg [ PDB-ID 3HRK; see also 3HRJ with L-histidine bound]

		Cpar071490AAB Cryptosporidium parvum tryptophanyl-tRNA synthetase With L-tryptophan from co-crystallization [ PDB-ID 3HV0 ]

		Gint015983AAC Giardia lamblia Prolyl-tRNA synthetase With prolyladenylate and inorganic phosphate bound after cocrystallization with L-proline and ATP. [ PDB-ID 3IAL ]

Category 4
Structures with metabolite ligands donated by E. coli

		Pfal004546AAA Plasmodium falciparum 6-pyruvoyl tetrahydrobiopterin synthase (PTPS) The blue electrondensity map surrounding biopterin is in magenta the 5 sigma anomalous difference map of a nearby zinc ion is clearly visible. [ PDB-ID 1Y13 ] [ PDB-ID 2A0S ] P. vivax
		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 ]

		Tbru015978AAA Trypanosoma brucei Dihydro orotate dehydrogenase Left: density for the FMN bound to Tbru015978AAA. Right: the orotate and FMN bound to Tbru015978AAA.

		Lmaj004144AAA Leishmania major Kinase with distant sequence homology to the nuclear AK6 The electron density 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 ]

		Lmaj004091AAA Leishmania major Methyl-transferase for an unknown substrate Member of Pfam family 05891/DUF858. We could identify Se-adenosyl-selenohomocysteine as cofactor due to large anomalous differences at the expected sulfur site. [ PDB-ID 1XTP ]

Category 5
Structures with surprise Ligands

Pfal007254AAA
Plasmodium falciparum
Glyceraldehyde-3-phosphate dehydrogenase
Close up view from the active site region. 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.

Robien, et al., (2006)
Proteins 62: 570-577

Additional Pathogenic Protozoan Structures with Ligands Solved by MSGPP Members

Category 2:	Structures with synthetic inhibitors
Category 3 & 4:	Structures with added metabolite Ligands

Category 2
Structures with synthetic inhibitors

		Peptide deformylase Plasmodium falciparum 2 (R)-[(fromyl-hydroxyamino)-methyl] hexanoic acid [ PDB-ID 1RI4 ] Robien, Mark A., Nguyen, K.T., Kumar, A., Hirsh, I., Turley, S., Pei, D., Hol, W.G.J. Protein Sci. (2004) 13: 1155-1163

		Phosphoglycerate kinase Trypanosoma brucei 2-amino-N⁶-[2"-(p-hydroxyphenyl)ethyl]adenosine (46b) J.C. Bressi,J . Choe, M.T. Hough, F.S. Buckner, W.C. Van Voorhis, C.L.M.J. Verlinde, W.G.J. Hol, M.H. Gelb J. Med. Chem. (2000) 43: 4135-4150
		Trypanosomatid glyceraldehyde-3-phosphate dehydrogenase Trypanosoma brucei, Trypanosoma cruzi and Leishmania mexicana N⁶-benzyl-NAD⁺ [ PDB-ID 1GYQ ] A.M. Aronov, S. Suresh, F.S. Buckner, W.C. van Voorhis, C.L.M.J. Verlinde, W.G.J. Hol, M.H. Gelb Proc. Natl. Acad. Sci. USA (1999) 96: 4273-4278
		Phosphoglycerate kinase Trypanosoma brucei Bisubstrate analog 1,1,5,5-tetrafluoropentane-1,5-bisphosphonate [ PDB-ID 16PK ] B.E. Bernstein, D.M. Williams, J.C. Bressi, P. Kuhn, M.H. Gelb, G.M. Blackburn, W.G.J. Hol J. Mol. Biol. (1998) 279: 1137-1148
		Phosphoglycerate kinase Trypanosoma brucei Substrate analog MgAMPPNP B.E. Bernstein, W.G.J. Hol Biochemistry (1998) 37: 4429-4436
		Trypanosomal Triosephosphate Isomerase Trypanosoma brucei N-hydroxy_4_phosphono_butanamide (4BPH) [ PDB-ID 1TSI ] C.L.M.J. Verlinde, C.J. Witmans, T. Pijning, K.H. Kalk, W.G.J. Hol, M. Callens, F.R. Opperdoes Protein Science (1992) 1: 1578-1584
		Trypanosomal Triosephosphate Isomerase Trypanosoma brucei 3-phosphonopropionic acid (3PP) [ PDB-ID 1IIG ] M.E.M. Noble, R.K. Wierenga, A.M. Lambeir, F.R. Opperdoes, A.M.W.H. Thunnissen, K.H. Kalk, H. Groendijk, W.G.J. Hol Proteins (1991) 10: 50-69
		Trypanosomal Triosephosphate Isomerase Trypanosoma brucei Glycerol-3-phosphate (G3P) [ PDB-ID 6TIM ] M.E.M. Noble, R.K. Wierenga, A.M. Lambeir, F.R. Opperdoes, A.M.W.H. Thunnissen, K.H. Kalk, H. Groendijk, W.G.J. Hol Proteins (1991) 10: 50-69
		Trypanosomal Triosephosphate Isomerase Trypanosoma brucei 3-phosphoglycerate (3-PGA) [ PDB-ID 1IIH ] M.E.M. Noble, R.K. Wierenga, A.M. Lambeir, F.R. Opperdoes, A.M.W.H. Thunnissen, K.H. Kalk, H. Groendijk, W.G.J. Hol Proteins (1991) 10: 50-69
		Trypanosomal Triosephosphate Isomerase Trypanosoma brucei 3-phosphonopropionic acid (3PP) M.E.M. Noble, C.L.M.J. Verlinde, H. Groendijk,K.H. Kalk, R.K. Wierenga, W.G.J. Hol J.Med. Chem. (1991) 34: 2709-2718

		Glycerol-3-phosphate Dehydrogenase Leishmania mexicana BCP, BOP,2-flouro-6-chloro-purine (FCP) and NADH J. Choe, S. Suresh, G. Wisedchaisri, K.J. Kennedy, M.H. Gelb, W.G.J. Hol Chem. & Biol. (2002) 8: 1189-1197
		Glycerol-3-phosphate Dehydrogenase Leishmania mexicana 2-bromo-6-hydroxy-purine (BOP) [ PDB-ID 1M67 ] J. Choe, S. Suresh, G. Wisedchaisri, K.J. Kennedy, M.H. Gelb, W.G.J. Hol Chem. & Biol. (2002) 8: 1189-1197
		Glycerol-3-phosphate Dehydrogenase Leishmania mexicana 2-bromo-6-chloro-purine (BCP) [ PDB-ID 1M66 ] J. Choe, S. Suresh, G. Wisedchaisri, K.J. Kennedy, M.H. Gelb, W.G.J. Hol Chem. & Biol. (2002) 8: 1189-1197
		Glyceraldehyde-3-phosphate Dehydrogenase Leishmania mexicana N⁶-(1-naphthalene methyl)-2'-deoxy-2"-(3,5-dimethoxy benzamido) adenosine (NMDBA) [ PDB-ID 1I32 ] S. Suresh, J.C. Bressi, K.J. Kennedy, C.L.M.J. Verlinde, M.H. Gelb, W.G.J. Hol J. Mol. Biol. (2001) 309: 423-435
		Glyceraldehyde-3-phosphate Dehydrogenase Leishmania mexicana N⁶-(1-naphthalene methyl)-2'-deoxy-2"-(3,5-dimethoxy benzamido) adenosine (NMDBA) [ PDB-ID 1I32 ] S. Suresh, J.C. Bressi, K.J. Kennedy, C.L.M.J. Verlinde, M.H. Gelb, W.G.J. Hol J. Mol. Biol. (2001) 309: 423-435
		Glyceraldehyde-3-phosphate Dehydrogenase Leishmania mexicana N⁶-(1,2,3,4-tetreahydronaphthyl)-2'-deoxy-2'-(3,5-dimethoxy benzamido) adenosine (TNDBA) [ PDB-ID 1I33 ] S. Suresh, J.C. Bressi, K.J. Kennedy, C.L.M.J. Verlinde, M.H. Gelb, W.G.J. Hol J. Mol. Biol. (2001) 309: 423-435

Category 3 and 4
Structures with metabolite Ligands

		Aldolase Plasmodium falciparum TRAP tripeptide [ PDB-ID 2PC4 ] [ PDB-ID 2EPH ] Bosch, J., Buscaglia, Carlos A., Krumm, Brian E., Ingason, B., Lucas, R., Roach, C., Cardozo, T., Nussenzweig, Victor, Hol, W. G. Proc. Natl. Acad. Sci. USA (2007) 104: 7015-7020

		Uridylyl transferase 2 Trypansoma brucei UTP [ PDB-ID 2B4V ] Deng, J., Lewis Ernst, N., Turley, S., Stuart, K. & Hol, W. G. J. EMBO J. (2005) 24: 4007-4017
		RNA Editing Ligase 1 Trypansoma brucei ATP Deng, J., Schnaufer, A., Salavati, R., Stuart, K. and Hol, W. G. J. J. Mol. Biol. (2004) 343: 601-613
		Phosphoglycerate kinase Trypanosoma brucei 3-phospho-glycerate (3-PGA) and Mg-ADP [ PDB-ID 13PK ] B.E. Bernstein, W.G.J. Hol Biochemistry (1998) 37: 4429-4436 B.E. Bernstein, P.A.M. Michels, W.G.J. Hol Nature (1997) 385: 275-278
		Phosphoglycerate kinase Trypanosoma brucei Pi and Mg-ADP B.E. Bernstein, W.G.J. Hol Biochemistry (1998) 37: 4429-4436
		Trypanosomal Glyceraldehyde-3-phosphate dehydrogenase Trypanosoma brucei NAD [ PDB-ID 1GGA ] C.L.M.J. Verlinde, M. Callens, S. Van Calenbergh, A. Van Aerschot, P. Herdewijn, V. Hannaert, P.A.M. Michels, F.R. Opperdoes, W.G.J. Hol J. Med. Chem. (1994) 37: 3605-3613 F.M.D. Vellieux, J. Hadju, W.G.J. Hol Acta Cryst (1995) D51: 575-589 F.M.D. Vellieux, J. Hadju, C.L.M.J. Verlinde, H. Groendijk, R.J. Read, T. Greenough, J.W. Campbell, K.H. Kalk, J. Littlechild, H.C. Watson, W.G.J. Hol Proc. Natl. Acad. Sci. USA (1993) 90: 2355-2359

		Glycerol-3-Phosphate Dehydrogenase Leishmania mexicana Adduct of dihydroxyacetone phosphate (DHAP) and NAD+ [ PDB-ID 1N1E ] J. Choe, Daniel Guerra, P.A.M. Michels, W.G.J. Hol J. Mol. Biol. (2003) 329: 335-349
		NAD-dependent glycerol-3-phosphate dehydrogenase Leishmania mexicana NADH [ PDB-ID 1EVY ] [ PDB-ID 1EVZ ] S. Suresh, T. Drmota, S. Turley, F.R. Opperdoes, P.A.M. Michels, W.G.J. Hol Structure Fold Des. (2000) 8: 542-552
		Glycosomal Glyceraldehyde-3-Phosphate Dehydrogenase Leishmania mexicana NAD [ PDB-ID 1GYP ] H. Kim, I.K. Feil, C.L.M.J. Verlinde, P.H. Petra, W.G.J. Hol Biochemistry (1995) 34: 14975-14986
		Topoisomerase I Leishmania donovani DNA [ PDB-ID 2B9S ] Davies, D.R., Mushtaq, A., Interthal, Heidrun, Champoux, James J., Hol, W.G.J. J. Mol. Biol. (2006) 24: 1202-1210