4RAD

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	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	0016740	molecular_function	transferase activity
A	0016757	molecular_function	glycosyltransferase activity
A	0032263	biological_process	GMP salvage
A	0032264	biological_process	IMP salvage
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	0046100	biological_process	hypoxanthine metabolic process
A	0046872	molecular_function	metal ion binding
A	0051289	biological_process	protein homotetramerization
A	0052657	molecular_function	guanine phosphoribosyltransferase activity
A	0070062	cellular_component	extracellular exosome
B	0000166	molecular_function	nucleotide binding
B	0000287	molecular_function	magnesium ion binding
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	0016740	molecular_function	transferase activity
B	0016757	molecular_function	glycosyltransferase activity
B	0032263	biological_process	GMP salvage
B	0032264	biological_process	IMP salvage
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	0046100	biological_process	hypoxanthine metabolic process
B	0046872	molecular_function	metal ion binding
B	0051289	biological_process	protein homotetramerization
B	0052657	molecular_function	guanine phosphoribosyltransferase activity
B	0070062	cellular_component	extracellular exosome
C	0000166	molecular_function	nucleotide binding
C	0000287	molecular_function	magnesium ion binding
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	0016740	molecular_function	transferase activity
C	0016757	molecular_function	glycosyltransferase activity
C	0032263	biological_process	GMP salvage
C	0032264	biological_process	IMP salvage
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	0046100	biological_process	hypoxanthine metabolic process
C	0046872	molecular_function	metal ion binding
C	0051289	biological_process	protein homotetramerization
C	0052657	molecular_function	guanine phosphoribosyltransferase activity
C	0070062	cellular_component	extracellular exosome
D	0000166	molecular_function	nucleotide binding
D	0000287	molecular_function	magnesium ion binding
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	0016740	molecular_function	transferase activity
D	0016757	molecular_function	glycosyltransferase activity
D	0032263	biological_process	GMP salvage
D	0032264	biological_process	IMP salvage
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	0046100	biological_process	hypoxanthine metabolic process
D	0046872	molecular_function	metal ion binding
D	0051289	biological_process	protein homotetramerization
D	0052657	molecular_function	guanine phosphoribosyltransferase activity
D	0070062	cellular_component	extracellular exosome
E	0000166	molecular_function	nucleotide binding
E	0000287	molecular_function	magnesium ion binding
E	0004422	molecular_function	hypoxanthine phosphoribosyltransferase activity
E	0005515	molecular_function	protein binding
E	0005737	cellular_component	cytoplasm
E	0005829	cellular_component	cytosol
E	0006164	biological_process	purine nucleotide biosynthetic process
E	0006166	biological_process	purine ribonucleoside salvage
E	0006178	biological_process	guanine salvage
E	0016740	molecular_function	transferase activity
E	0016757	molecular_function	glycosyltransferase activity
E	0032263	biological_process	GMP salvage
E	0032264	biological_process	IMP salvage
E	0042802	molecular_function	identical protein binding
E	0043103	biological_process	hypoxanthine salvage
E	0044209	biological_process	AMP salvage
E	0045964	biological_process	positive regulation of dopamine metabolic process
E	0046038	biological_process	GMP catabolic process
E	0046040	biological_process	IMP metabolic process
E	0046100	biological_process	hypoxanthine metabolic process
E	0046872	molecular_function	metal ion binding
E	0051289	biological_process	protein homotetramerization
E	0052657	molecular_function	guanine phosphoribosyltransferase activity
E	0070062	cellular_component	extracellular exosome
F	0000166	molecular_function	nucleotide binding
F	0000287	molecular_function	magnesium ion binding
F	0004422	molecular_function	hypoxanthine phosphoribosyltransferase activity
F	0005515	molecular_function	protein binding
F	0005737	cellular_component	cytoplasm
F	0005829	cellular_component	cytosol
F	0006164	biological_process	purine nucleotide biosynthetic process
F	0006166	biological_process	purine ribonucleoside salvage
F	0006178	biological_process	guanine salvage
F	0016740	molecular_function	transferase activity
F	0016757	molecular_function	glycosyltransferase activity
F	0032263	biological_process	GMP salvage
F	0032264	biological_process	IMP salvage
F	0042802	molecular_function	identical protein binding
F	0043103	biological_process	hypoxanthine salvage
F	0044209	biological_process	AMP salvage
F	0045964	biological_process	positive regulation of dopamine metabolic process
F	0046038	biological_process	GMP catabolic process
F	0046040	biological_process	IMP metabolic process
F	0046100	biological_process	hypoxanthine metabolic process
F	0046872	molecular_function	metal ion binding
F	0051289	biological_process	protein homotetramerization
F	0052657	molecular_function	guanine phosphoribosyltransferase activity
F	0070062	cellular_component	extracellular exosome
G	0000166	molecular_function	nucleotide binding
G	0000287	molecular_function	magnesium ion binding
G	0004422	molecular_function	hypoxanthine phosphoribosyltransferase activity
G	0005515	molecular_function	protein binding
G	0005737	cellular_component	cytoplasm
G	0005829	cellular_component	cytosol
G	0006164	biological_process	purine nucleotide biosynthetic process
G	0006166	biological_process	purine ribonucleoside salvage
G	0006178	biological_process	guanine salvage
G	0016740	molecular_function	transferase activity
G	0016757	molecular_function	glycosyltransferase activity
G	0032263	biological_process	GMP salvage
G	0032264	biological_process	IMP salvage
G	0042802	molecular_function	identical protein binding
G	0043103	biological_process	hypoxanthine salvage
G	0044209	biological_process	AMP salvage
G	0045964	biological_process	positive regulation of dopamine metabolic process
G	0046038	biological_process	GMP catabolic process
G	0046040	biological_process	IMP metabolic process
G	0046100	biological_process	hypoxanthine metabolic process
G	0046872	molecular_function	metal ion binding
G	0051289	biological_process	protein homotetramerization
G	0052657	molecular_function	guanine phosphoribosyltransferase activity
G	0070062	cellular_component	extracellular exosome
H	0000166	molecular_function	nucleotide binding
H	0000287	molecular_function	magnesium ion binding
H	0004422	molecular_function	hypoxanthine phosphoribosyltransferase activity
H	0005515	molecular_function	protein binding
H	0005737	cellular_component	cytoplasm
H	0005829	cellular_component	cytosol
H	0006164	biological_process	purine nucleotide biosynthetic process
H	0006166	biological_process	purine ribonucleoside salvage
H	0006178	biological_process	guanine salvage
H	0016740	molecular_function	transferase activity
H	0016757	molecular_function	glycosyltransferase activity
H	0032263	biological_process	GMP salvage
H	0032264	biological_process	IMP salvage
H	0042802	molecular_function	identical protein binding
H	0043103	biological_process	hypoxanthine salvage
H	0044209	biological_process	AMP salvage
H	0045964	biological_process	positive regulation of dopamine metabolic process
H	0046038	biological_process	GMP catabolic process
H	0046040	biological_process	IMP metabolic process
H	0046100	biological_process	hypoxanthine metabolic process
H	0046872	molecular_function	metal ion binding
H	0051289	biological_process	protein homotetramerization
H	0052657	molecular_function	guanine phosphoribosyltransferase activity
H	0070062	cellular_component	extracellular exosome

Functional Information from PDB Data

site_id	AC1
Number of Residues	17
Details	BINDING SITE FOR RESIDUE 3L5 A 301

Chain	Residue
A	LYS68
A	LYS165
A	LYS185
A	PHE186
A	VAL187
A	ASP193
A	ARG199
A	HOH402
A	HOH446
A	GLY69
A	ILE135
A	ILE136
A	ASP137
A	THR138
A	GLY139
A	LYS140
A	THR141

---

site_id	AC2
Number of Residues	3
Details	BINDING SITE FOR RESIDUE MG A 302

Chain	Residue
A	GLU133
A	ILE135
A	THR141

---

site_id	AC3
Number of Residues	17
Details	BINDING SITE FOR RESIDUE 3L5 B 301

Chain	Residue
B	ILE135
B	ASP137
B	THR138
B	GLY139
B	LYS140
B	THR141
B	LYS165
B	LYS185
B	PHE186
B	VAL187
B	ASP193
B	MG303
B	HOH406
B	HOH420
B	HOH463
B	HOH475
B	HOH484

---

site_id	AC4
Number of Residues	4
Details	BINDING SITE FOR RESIDUE MG B 302

Chain	Residue
B	GLU133
B	ASP134
B	ILE135
B	THR141

---

site_id	AC5
Number of Residues	5
Details	BINDING SITE FOR RESIDUE MG B 303

Chain	Residue
B	ASP193
B	3L5301
B	HOH463
B	HOH471
B	HOH484

---

site_id	AC6
Number of Residues	22
Details	BINDING SITE FOR RESIDUE 3L5 C 301

Chain	Residue
C	LYS68
C	GLY69
C	ASP134
C	ILE135
C	ASP137
C	THR138
C	GLY139
C	LYS140
C	THR141
C	LYS165
C	LYS185
C	PHE186
C	VAL187
C	ALA191
C	LEU192
C	ASP193
C	ARG199
C	HOH418
C	HOH439
C	HOH466
C	HOH468
C	HOH470

---

site_id	AC7
Number of Residues	6
Details	BINDING SITE FOR RESIDUE MG C 302

Chain	Residue
C	GLU133
C	ASP134
C	HOH466
C	HOH467
C	HOH468
C	HOH469

---

site_id	AC8
Number of Residues	24
Details	BINDING SITE FOR RESIDUE 3L5 D 301

Chain	Residue
D	LEU67
D	LYS68
D	GLY69
D	ASP134
D	ILE135
D	ASP137
D	THR138
D	GLY139
D	LYS140
D	THR141
D	LYS165
D	LYS185
D	PHE186
D	VAL187
D	ASP193
D	ARG199
D	MG302
D	HOH427
D	HOH456
D	HOH466
D	HOH475
D	HOH478
D	HOH492
D	HOH493

---

site_id	AC9
Number of Residues	6
Details	BINDING SITE FOR RESIDUE MG D 302

Chain	Residue
D	ASP134
D	3L5301
D	HOH492
D	HOH493
D	HOH494
D	GLU133

---

site_id	BC1
Number of Residues	19
Details	BINDING SITE FOR RESIDUE 3L5 E 301

Chain	Residue
E	LYS68
E	GLY69
E	ASP134
E	ILE135
E	ASP137
E	THR138
E	GLY139
E	LYS140
E	THR141
E	LYS165
E	LYS185
E	PHE186
E	VAL187
E	ASP193
E	ARG199
E	HOH415
E	HOH427
E	HOH439
E	HOH440

---

site_id	BC2
Number of Residues	25
Details	BINDING SITE FOR RESIDUE 3L5 F 301

Chain	Residue
F	LYS102
F	SER103
F	ILE135
F	ASP137
F	THR138
F	GLY139
F	LYS140
F	THR141
F	LYS165
F	LYS185
F	PHE186
F	VAL187
F	ASP193
F	MG302
F	MG303
F	HOH406
F	HOH412
F	HOH414
F	HOH423
F	HOH427
F	HOH429
F	HOH432
F	HOH437
F	HOH461
F	HOH467

---

site_id	BC3
Number of Residues	6
Details	BINDING SITE FOR RESIDUE MG F 302

Chain	Residue
F	GLU133
F	ASP134
F	ILE135
F	THR141
F	3L5301
F	HOH472

---

site_id	BC4
Number of Residues	4
Details	BINDING SITE FOR RESIDUE MG F 303

Chain	Residue
F	ASP193
F	3L5301
F	HOH437
F	HOH488

---

site_id	BC5
Number of Residues	13
Details	BINDING SITE FOR RESIDUE 3L5 G 301

Chain	Residue
G	ILE135
G	ILE136
G	ASP137
G	THR138
G	GLY139
G	LYS140
G	THR141
G	LYS165
G	LYS185
G	PHE186
G	VAL187
G	ASP193
G	MG302

---

site_id	BC6
Number of Residues	5
Details	BINDING SITE FOR RESIDUE MG G 302

Chain	Residue
G	GLU133
G	ASP134
G	3L5301
G	HOH433
G	HOH435

---

site_id	BC7
Number of Residues	21
Details	BINDING SITE FOR RESIDUE 3L5 H 301

Chain	Residue
H	LYS68
H	GLY69
H	ARG100
H	ILE135
H	ASP137
H	THR138
H	GLY139
H	LYS140
H	THR141
H	LYS165
H	LYS185
H	PHE186
H	VAL187
H	ASP193
H	ARG199
H	MG302
H	HOH420
H	HOH423
H	HOH436
H	HOH449
H	HOH451

---

site_id	BC8
Number of Residues	6
Details	BINDING SITE FOR RESIDUE MG H 302

Chain	Residue
H	GLU133
H	ASP134
H	3L5301
H	HOH406
H	HOH449
H	HOH451

---

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	8
Details	Active site: {"description":"Proton acceptor","evidences":[{"evidenceCode":"ECO:0000305"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI2
Number of Residues	96
Details	Binding site: {"evidences":[{"source":"PubMed","id":"8044844","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI3
Number of Residues	8
Details	Binding site: {}

Chain

Residue

Details

---

site_id	SWS_FT_FI4
Number of Residues	8
Details	Modified residue: {"description":"Phosphothreonine","evidences":[{"source":"UniProtKB","id":"P27605","evidenceCode":"ECO:0000250"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI5
Number of Residues	6
Details	Modified residue: {"description":"N6-acetyllysine","evidences":[{"source":"UniProtKB","id":"P00493","evidenceCode":"ECO:0000250"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI6
Number of Residues	14
Details	Cross-link: {"description":"Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate","evidences":[{"source":"PubMed","id":"28112733","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---

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

---

site_id	MCSA5
Number of Residues	5
Details	M-CSA 48

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

---

site_id	MCSA6
Number of Residues	5
Details	M-CSA 48

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

---

site_id	MCSA7
Number of Residues	5
Details	M-CSA 48

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

---

site_id	MCSA8
Number of Residues	5
Details	M-CSA 48

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

---