Summary Structural details Experimental details Functional details Sequence Neighbor History Downloads

4RAC

Aza-acyclic nucleoside phosphonates containing a second phosphonate group as inhibitors of the human, Plasmodium falciparum and vivax 6-oxopurine phosphoribosyltransferases and their pro-drugs as antimalarial agents

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0000166	molecular_function	nucleotide binding
A	0000287	molecular_function	magnesium ion binding
A	0001913	biological_process	T cell mediated cytotoxicity
A	0001975	biological_process	response to amphetamine
A	0004422	molecular_function	hypoxanthine phosphoribosyltransferase activity
A	0005515	molecular_function	protein binding
A	0005737	cellular_component	cytoplasm
A	0005829	cellular_component	cytosol
A	0006164	biological_process	purine nucleotide biosynthetic process
A	0006166	biological_process	purine ribonucleoside salvage
A	0006178	biological_process	guanine salvage
A	0007625	biological_process	grooming behavior
A	0007626	biological_process	locomotory behavior
A	0016757	molecular_function	glycosyltransferase activity
A	0021756	biological_process	striatum development
A	0021895	biological_process	cerebral cortex neuron differentiation
A	0021954	biological_process	central nervous system neuron development
A	0032263	biological_process	GMP salvage
A	0032264	biological_process	IMP salvage
A	0042417	biological_process	dopamine metabolic process
A	0042802	molecular_function	identical protein binding
A	0043103	biological_process	hypoxanthine salvage
A	0044209	biological_process	AMP salvage
A	0045964	biological_process	positive regulation of dopamine metabolic process
A	0046038	biological_process	GMP catabolic process
A	0046040	biological_process	IMP metabolic process
A	0046083	biological_process	adenine metabolic process
A	0046100	biological_process	hypoxanthine metabolic process
A	0046651	biological_process	lymphocyte proliferation
A	0046872	molecular_function	metal ion binding
A	0048813	biological_process	dendrite morphogenesis
A	0051289	biological_process	protein homotetramerization
A	0052657	molecular_function	guanine phosphoribosyltransferase activity
A	0070062	cellular_component	extracellular exosome
A	0071542	biological_process	dopaminergic neuron differentiation
B	0000166	molecular_function	nucleotide binding
B	0000287	molecular_function	magnesium ion binding
B	0001913	biological_process	T cell mediated cytotoxicity
B	0001975	biological_process	response to amphetamine
B	0004422	molecular_function	hypoxanthine phosphoribosyltransferase activity
B	0005515	molecular_function	protein binding
B	0005737	cellular_component	cytoplasm
B	0005829	cellular_component	cytosol
B	0006164	biological_process	purine nucleotide biosynthetic process
B	0006166	biological_process	purine ribonucleoside salvage
B	0006178	biological_process	guanine salvage
B	0007625	biological_process	grooming behavior
B	0007626	biological_process	locomotory behavior
B	0016757	molecular_function	glycosyltransferase activity
B	0021756	biological_process	striatum development
B	0021895	biological_process	cerebral cortex neuron differentiation
B	0021954	biological_process	central nervous system neuron development
B	0032263	biological_process	GMP salvage
B	0032264	biological_process	IMP salvage
B	0042417	biological_process	dopamine metabolic process
B	0042802	molecular_function	identical protein binding
B	0043103	biological_process	hypoxanthine salvage
B	0044209	biological_process	AMP salvage
B	0045964	biological_process	positive regulation of dopamine metabolic process
B	0046038	biological_process	GMP catabolic process
B	0046040	biological_process	IMP metabolic process
B	0046083	biological_process	adenine metabolic process
B	0046100	biological_process	hypoxanthine metabolic process
B	0046651	biological_process	lymphocyte proliferation
B	0046872	molecular_function	metal ion binding
B	0048813	biological_process	dendrite morphogenesis
B	0051289	biological_process	protein homotetramerization
B	0052657	molecular_function	guanine phosphoribosyltransferase activity
B	0070062	cellular_component	extracellular exosome
B	0071542	biological_process	dopaminergic neuron differentiation
C	0000166	molecular_function	nucleotide binding
C	0000287	molecular_function	magnesium ion binding
C	0001913	biological_process	T cell mediated cytotoxicity
C	0001975	biological_process	response to amphetamine
C	0004422	molecular_function	hypoxanthine phosphoribosyltransferase activity
C	0005515	molecular_function	protein binding
C	0005737	cellular_component	cytoplasm
C	0005829	cellular_component	cytosol
C	0006164	biological_process	purine nucleotide biosynthetic process
C	0006166	biological_process	purine ribonucleoside salvage
C	0006178	biological_process	guanine salvage
C	0007625	biological_process	grooming behavior
C	0007626	biological_process	locomotory behavior
C	0016757	molecular_function	glycosyltransferase activity
C	0021756	biological_process	striatum development
C	0021895	biological_process	cerebral cortex neuron differentiation
C	0021954	biological_process	central nervous system neuron development
C	0032263	biological_process	GMP salvage
C	0032264	biological_process	IMP salvage
C	0042417	biological_process	dopamine metabolic process
C	0042802	molecular_function	identical protein binding
C	0043103	biological_process	hypoxanthine salvage
C	0044209	biological_process	AMP salvage
C	0045964	biological_process	positive regulation of dopamine metabolic process
C	0046038	biological_process	GMP catabolic process
C	0046040	biological_process	IMP metabolic process
C	0046083	biological_process	adenine metabolic process
C	0046100	biological_process	hypoxanthine metabolic process
C	0046651	biological_process	lymphocyte proliferation
C	0046872	molecular_function	metal ion binding
C	0048813	biological_process	dendrite morphogenesis
C	0051289	biological_process	protein homotetramerization
C	0052657	molecular_function	guanine phosphoribosyltransferase activity
C	0070062	cellular_component	extracellular exosome
C	0071542	biological_process	dopaminergic neuron differentiation
D	0000166	molecular_function	nucleotide binding
D	0000287	molecular_function	magnesium ion binding
D	0001913	biological_process	T cell mediated cytotoxicity
D	0001975	biological_process	response to amphetamine
D	0004422	molecular_function	hypoxanthine phosphoribosyltransferase activity
D	0005515	molecular_function	protein binding
D	0005737	cellular_component	cytoplasm
D	0005829	cellular_component	cytosol
D	0006164	biological_process	purine nucleotide biosynthetic process
D	0006166	biological_process	purine ribonucleoside salvage
D	0006178	biological_process	guanine salvage
D	0007625	biological_process	grooming behavior
D	0007626	biological_process	locomotory behavior
D	0016757	molecular_function	glycosyltransferase activity
D	0021756	biological_process	striatum development
D	0021895	biological_process	cerebral cortex neuron differentiation
D	0021954	biological_process	central nervous system neuron development
D	0032263	biological_process	GMP salvage
D	0032264	biological_process	IMP salvage
D	0042417	biological_process	dopamine metabolic process
D	0042802	molecular_function	identical protein binding
D	0043103	biological_process	hypoxanthine salvage
D	0044209	biological_process	AMP salvage
D	0045964	biological_process	positive regulation of dopamine metabolic process
D	0046038	biological_process	GMP catabolic process
D	0046040	biological_process	IMP metabolic process
D	0046083	biological_process	adenine metabolic process
D	0046100	biological_process	hypoxanthine metabolic process
D	0046651	biological_process	lymphocyte proliferation
D	0046872	molecular_function	metal ion binding
D	0048813	biological_process	dendrite morphogenesis
D	0051289	biological_process	protein homotetramerization
D	0052657	molecular_function	guanine phosphoribosyltransferase activity
D	0070062	cellular_component	extracellular exosome
D	0071542	biological_process	dopaminergic neuron differentiation

Functional Information from PDB Data

site_id	AC1
Number of Residues	28
Details	BINDING SITE FOR RESIDUE 3L4 A 301

Chain	Residue
A	LEU67
A	LYS165
A	LYS185
A	PHE186
A	VAL187
A	LEU192
A	ASP193
A	ARG199
A	MG302
A	HOH401
A	HOH402
A	LYS68
A	HOH403
A	HOH410
A	HOH411
A	HOH416
A	HOH420
A	HOH433
A	HOH435
A	HOH438
A	HOH456
A	GLY69
A	LEU101
A	ASP137
A	THR138
A	GLY139
A	LYS140
A	THR141

site_id	AC2
Number of Residues	6
Details	BINDING SITE FOR RESIDUE MG A 302

Chain	Residue
A	ASP193
A	3L4301
A	HOH416
A	HOH417
A	HOH420
A	HOH456

site_id	AC3
Number of Residues	6
Details	BINDING SITE FOR RESIDUE MG A 303

Chain	Residue
A	GLU133
A	ASP134
A	HOH401
A	HOH402
A	HOH406
A	HOH408

site_id	AC4
Number of Residues	25
Details	BINDING SITE FOR RESIDUE 3L4 B 301

Chain	Residue
B	LEU67
B	LYS68
B	GLY69
B	LEU101
B	ASP137
B	THR138
B	GLY139
B	LYS140
B	THR141
B	LYS165
B	LYS185
B	PHE186
B	VAL187
B	LEU192
B	ASP193
B	ARG199
B	MG302
B	HOH402
B	HOH403
B	HOH413
B	HOH416
B	HOH419
B	HOH439
B	HOH446
B	HOH457

site_id	AC5
Number of Residues	6
Details	BINDING SITE FOR RESIDUE MG B 302

Chain	Residue
B	ASP193
B	3L4301
B	HOH406
B	HOH409
B	HOH419
B	HOH457

site_id	AC6
Number of Residues	6
Details	BINDING SITE FOR RESIDUE MG B 303

Chain	Residue
B	GLU133
B	ASP134
B	HOH402
B	HOH434
B	HOH446
B	HOH448

site_id	AC7
Number of Residues	27
Details	BINDING SITE FOR RESIDUE 3L4 C 301

Chain	Residue
C	HOH415
C	HOH422
C	HOH428
C	HOH432
C	HOH456
C	LEU67
C	LYS68
C	GLY69
C	ILE135
C	ASP137
C	THR138
C	GLY139
C	LYS140
C	THR141
C	LYS165
C	LYS185
C	PHE186
C	VAL187
C	LEU192
C	ASP193
C	ARG199
C	MG303
C	HOH401
C	HOH403
C	HOH411
C	HOH412
C	HOH414

site_id	AC8
Number of Residues	6
Details	BINDING SITE FOR RESIDUE MG C 302

Chain	Residue
C	GLU133
C	ASP134
C	HOH401
C	HOH403
C	HOH404
C	HOH458

site_id	AC9
Number of Residues	6
Details	BINDING SITE FOR RESIDUE MG C 303

Chain	Residue
C	ASP193
C	3L4301
C	HOH412
C	HOH455
C	HOH456
C	HOH457

site_id	BC1
Number of Residues	14
Details	BINDING SITE FOR RESIDUE 3L4 D 301

Chain	Residue
D	LYS68
D	GLY69
D	ASP137
D	THR138
D	GLY139
D	THR141
D	LYS165
D	LYS185
D	PHE186
D	VAL187
D	ASP193
D	ARG199
D	HOH431
D	HOH432

site_id	BC2
Number of Residues	5
Details	BINDING SITE FOR RESIDUE MG D 302

Chain	Residue
D	GLU133
D	ASP134
D	HOH430
D	HOH431
D	HOH432

Functional Information from PROSITE/UniProt

site_id	PS00103
Number of Residues	13
Details	PUR_PYR_PR_TRANSFER Purine/pyrimidine phosphoribosyl transferases signature. VLIVEDIIDTGkT

Chain	Residue	Details
A	VAL129-THR141

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	4
Details	ACT_SITE: Proton acceptor => ECO:0000305

Chain	Residue	Details
A	ASP137
B	ASP137
C	ASP137
D	ASP137

site_id	SWS_FT_FI2
Number of Residues	16
Details	BINDING: BINDING => ECO:0000269\|PubMed:8044844

Chain	Residue	Details
A	LYS68
C	GLU133
C	LYS165
C	LYS185
D	LYS68
D	GLU133
D	LYS165
D	LYS185
A	GLU133
A	LYS165
A	LYS185
B	LYS68
B	GLU133
B	LYS165
B	LYS185
C	LYS68

site_id	SWS_FT_FI3
Number of Residues	4
Details	BINDING:

Chain	Residue	Details
A	ASP193
B	ASP193
C	ASP193
D	ASP193

site_id	SWS_FT_FI4
Number of Residues	4
Details	MOD_RES: N-acetylalanine => ECO:0000269\|PubMed:7107641

Chain	Residue	Details
A	ALA1
B	ALA1
C	ALA1
D	ALA1

site_id	SWS_FT_FI5
Number of Residues	4
Details	MOD_RES: N6-acetyllysine => ECO:0000250\|UniProtKB:P00493

Chain	Residue	Details
A	LYS102
B	LYS102
C	LYS102
D	LYS102

site_id	SWS_FT_FI6
Number of Residues	4
Details	MOD_RES: Phosphothreonine => ECO:0000250\|UniProtKB:P27605

Chain	Residue	Details
A	THR141
B	THR141
C	THR141
D	THR141

site_id	SWS_FT_FI7
Number of Residues	8
Details	CROSSLNK: Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate => ECO:0007744\|PubMed:28112733

Chain	Residue	Details
A	LYS114
B	LYS114
C	LYS114
D	LYS114

Catalytic Information from CSA

site_id	MCSA1
Number of Residues	5
Details	M-CSA 48

Chain	Residue	Details
A	GLU133	attractive charge-charge interaction, electrostatic stabiliser
A	ASP134	attractive charge-charge interaction, electrostatic stabiliser
A	ASP137	hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor
A	PHE186	electrostatic stabiliser
A	ARG199	electrostatic stabiliser

site_id	MCSA2
Number of Residues	5
Details	M-CSA 48

Chain	Residue	Details
B	GLU133	attractive charge-charge interaction, electrostatic stabiliser
B	ASP134	attractive charge-charge interaction, electrostatic stabiliser
B	ASP137	hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor
B	PHE186	electrostatic stabiliser
B	ARG199	electrostatic stabiliser

site_id	MCSA3
Number of Residues	5
Details	M-CSA 48

Chain	Residue	Details
C	GLU133	attractive charge-charge interaction, electrostatic stabiliser
C	ASP134	attractive charge-charge interaction, electrostatic stabiliser
C	ASP137	hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor
C	PHE186	electrostatic stabiliser
C	ARG199	electrostatic stabiliser

site_id	MCSA4
Number of Residues	5
Details	M-CSA 48

Chain	Residue	Details
D	GLU133	attractive charge-charge interaction, electrostatic stabiliser
D	ASP134	attractive charge-charge interaction, electrostatic stabiliser
D	ASP137	hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor
D	PHE186	electrostatic stabiliser
D	ARG199	electrostatic stabiliser

		Sequence (fasta)
		PDBx/mmCIF
		PDBML format (no-atom)
		PDB format (full)
		Validation report (PDF)
		EDMap 2fo-fc (MTZ)