Summary Structural details Experimental details Functional details Sequence Neighbor History Downloads

4X2T

X-ray crystal structure of the orally available aminopeptidase inhibitor, Tosedostat, bound to the M17 Leucyl Aminopeptidase from P. falciparum

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0005737	cellular_component	cytoplasm
A	0006508	biological_process	proteolysis
A	0019538	biological_process	protein metabolic process
A	0030145	molecular_function	manganese ion binding
A	0046872	molecular_function	metal ion binding
A	0070006	molecular_function	metalloaminopeptidase activity
B	0005737	cellular_component	cytoplasm
B	0006508	biological_process	proteolysis
B	0019538	biological_process	protein metabolic process
B	0030145	molecular_function	manganese ion binding
B	0046872	molecular_function	metal ion binding
B	0070006	molecular_function	metalloaminopeptidase activity
C	0005737	cellular_component	cytoplasm
C	0006508	biological_process	proteolysis
C	0019538	biological_process	protein metabolic process
C	0030145	molecular_function	manganese ion binding
C	0046872	molecular_function	metal ion binding
C	0070006	molecular_function	metalloaminopeptidase activity
D	0005737	cellular_component	cytoplasm
D	0006508	biological_process	proteolysis
D	0019538	biological_process	protein metabolic process
D	0030145	molecular_function	manganese ion binding
D	0046872	molecular_function	metal ion binding
D	0070006	molecular_function	metalloaminopeptidase activity
E	0005737	cellular_component	cytoplasm
E	0006508	biological_process	proteolysis
E	0019538	biological_process	protein metabolic process
E	0030145	molecular_function	manganese ion binding
E	0046872	molecular_function	metal ion binding
E	0070006	molecular_function	metalloaminopeptidase activity
F	0005737	cellular_component	cytoplasm
F	0006508	biological_process	proteolysis
F	0019538	biological_process	protein metabolic process
F	0030145	molecular_function	manganese ion binding
F	0046872	molecular_function	metal ion binding
F	0070006	molecular_function	metalloaminopeptidase activity
G	0005737	cellular_component	cytoplasm
G	0006508	biological_process	proteolysis
G	0019538	biological_process	protein metabolic process
G	0030145	molecular_function	manganese ion binding
G	0046872	molecular_function	metal ion binding
G	0070006	molecular_function	metalloaminopeptidase activity
H	0005737	cellular_component	cytoplasm
H	0006508	biological_process	proteolysis
H	0019538	biological_process	protein metabolic process
H	0030145	molecular_function	manganese ion binding
H	0046872	molecular_function	metal ion binding
H	0070006	molecular_function	metalloaminopeptidase activity
I	0005737	cellular_component	cytoplasm
I	0006508	biological_process	proteolysis
I	0019538	biological_process	protein metabolic process
I	0030145	molecular_function	manganese ion binding
I	0046872	molecular_function	metal ion binding
I	0070006	molecular_function	metalloaminopeptidase activity
J	0005737	cellular_component	cytoplasm
J	0006508	biological_process	proteolysis
J	0019538	biological_process	protein metabolic process
J	0030145	molecular_function	manganese ion binding
J	0046872	molecular_function	metal ion binding
J	0070006	molecular_function	metalloaminopeptidase activity
K	0005737	cellular_component	cytoplasm
K	0006508	biological_process	proteolysis
K	0019538	biological_process	protein metabolic process
K	0030145	molecular_function	manganese ion binding
K	0046872	molecular_function	metal ion binding
K	0070006	molecular_function	metalloaminopeptidase activity
L	0005737	cellular_component	cytoplasm
L	0006508	biological_process	proteolysis
L	0019538	biological_process	protein metabolic process
L	0030145	molecular_function	manganese ion binding
L	0046872	molecular_function	metal ion binding
L	0070006	molecular_function	metalloaminopeptidase activity

Functional Information from PDB Data

site_id	AC1
Number of Residues	5
Details	binding site for residue ZN A 701

Chain	Residue
A	ASP379
A	ASP459
A	GLU461
A	ZN702
A	TOD703

site_id	AC2
Number of Residues	6
Details	binding site for residue ZN A 702

Chain	Residue
A	ZN701
A	TOD703
A	LYS374
A	ASP379
A	ASP399
A	GLU461

site_id	AC3
Number of Residues	13
Details	binding site for residue TOD A 703

Chain	Residue
A	LYS374
A	ASP379
A	LYS386
A	ASP459
A	ALA460
A	GLU461
A	LEU487
A	GLY489
A	ZN701
A	ZN702
A	CO3704
A	HOH829
A	HOH830

site_id	AC4
Number of Residues	5
Details	binding site for residue CO3 A 704

Chain	Residue
A	ALA460
A	GLY462
A	ARG463
A	LEU487
A	TOD703

site_id	AC5
Number of Residues	6
Details	binding site for residue SO4 A 706

Chain	Residue
A	ASP249
A	TYR292
A	SER295
A	LYS587
A	PRO588
C	TYR541

site_id	AC6
Number of Residues	4
Details	binding site for residue SO4 A 707

Chain	Residue
A	ILE529
A	ILE530
A	ASN531
F	TYR499

site_id	AC7
Number of Residues	5
Details	binding site for residue 1PE A 708

Chain	Residue
A	TYR103
A	ASN104
A	HIS108
A	LYS320
A	TYR411

site_id	AC8
Number of Residues	7
Details	binding site for residue CO3 B 1001

Chain	Residue
B	LYS374
B	ALA460
B	GLU461
B	GLY462
B	ARG463
B	LEU487
B	TOD1004

site_id	AC9
Number of Residues	5
Details	binding site for residue ZN B 1002

Chain	Residue
B	ASP379
B	ASP459
B	GLU461
B	ZN1003
B	TOD1004

site_id	AD1
Number of Residues	6
Details	binding site for residue ZN B 1003

Chain	Residue
B	LYS374
B	ASP379
B	ASP399
B	GLU461
B	ZN1002
B	TOD1004

site_id	AD2
Number of Residues	11
Details	binding site for residue TOD B 1004

Chain	Residue
B	LYS374
B	ASP379
B	LYS386
B	ASP459
B	GLU461
B	LEU487
B	GLY489
B	ALA490
B	CO31001
B	ZN1002
B	ZN1003

site_id	AD3
Number of Residues	6
Details	binding site for residue SO4 B 1005

Chain	Residue
A	SER435
A	LYS436
B	SER435
B	LYS436
C	SER435
C	LYS436

site_id	AD4
Number of Residues	4
Details	binding site for residue 1PE B 1006

Chain	Residue
B	TYR103
B	HIS108
B	LYS320
B	TYR411

site_id	AD5
Number of Residues	6
Details	binding site for residue ZN C 701

Chain	Residue
C	LYS374
C	ASP379
C	ASP399
C	GLU461
C	ZN702
C	TOD703

site_id	AD6
Number of Residues	5
Details	binding site for residue ZN C 702

Chain	Residue
C	ASP379
C	ASP459
C	GLU461
C	ZN701
C	TOD703

site_id	AD7
Number of Residues	11
Details	binding site for residue TOD C 703

Chain	Residue
C	GLU461
C	LEU487
C	GLY489
C	ZN701
C	ZN702
C	CO3704
C	LYS374
C	ASP379
C	LYS386
C	ASN457
C	ASP459

site_id	AD8
Number of Residues	7
Details	binding site for residue CO3 C 704

Chain	Residue
C	LYS374
C	ALA460
C	GLU461
C	GLY462
C	ARG463
C	LEU487
C	TOD703

site_id	AD9
Number of Residues	3
Details	binding site for residue SO4 C 705

Chain	Residue
C	GLY126
C	LEU219
C	SER220

site_id	AE1
Number of Residues	6
Details	binding site for residue 1PE C 706

Chain	Residue
C	TYR103
C	GLU316
C	GLN319
C	LYS320
C	1PE707
C	HOH852

site_id	AE2
Number of Residues	6
Details	binding site for residue 1PE C 707

Chain	Residue
C	TYR103
C	ASN104
C	HIS108
C	LYS320
C	TYR411
C	1PE706

site_id	AE3
Number of Residues	4
Details	binding site for residue ZN D 701

Chain	Residue
D	ASP379
D	ASP459
D	GLU461
D	ZN702

site_id	AE4
Number of Residues	5
Details	binding site for residue ZN D 702

Chain	Residue
D	LYS374
D	ASP379
D	ASP399
D	GLU461
D	ZN701

site_id	AE5
Number of Residues	6
Details	binding site for residue CO3 D 703

Chain	Residue
D	LYS374
D	ALA460
D	GLU461
D	GLY462
D	ARG463
D	LEU487

site_id	AE6
Number of Residues	6
Details	binding site for residue SO4 D 704

Chain	Residue
A	PHE156
A	ASN161
D	TYR176
D	MET177
D	PHE178
D	SER184

site_id	AE7
Number of Residues	6
Details	binding site for residue 1PE D 705

Chain	Residue
D	TYR103
D	ASN104
D	HIS108
D	LYS320
D	TYR411
D	1PE706

site_id	AE8
Number of Residues	4
Details	binding site for residue 1PE D 706

Chain	Residue
D	TYR103
D	GLU316
D	LYS320
D	1PE705

site_id	AE9
Number of Residues	6
Details	binding site for residue ZN E 701

Chain	Residue
E	LYS374
E	ASP379
E	ASP399
E	GLU461
E	ZN702
E	TOD703

site_id	AF1
Number of Residues	5
Details	binding site for residue ZN E 702

Chain	Residue
E	ASP379
E	ASP459
E	GLU461
E	ZN701
E	TOD703

site_id	AF2
Number of Residues	12
Details	binding site for residue TOD E 703

Chain	Residue
E	LYS374
E	ASP379
E	LYS386
E	ASP399
E	ASP459
E	GLU461
E	LEU487
E	THR488
E	GLY489
E	ZN701
E	ZN702
E	CO3704

site_id	AF3
Number of Residues	6
Details	binding site for residue CO3 E 704

Chain	Residue
E	LYS374
E	ALA460
E	GLY462
E	ARG463
E	LEU487
E	TOD703

site_id	AF4
Number of Residues	6
Details	binding site for residue SO4 E 705

Chain	Residue
D	SER435
D	LYS436
E	SER435
E	LYS436
F	SER435
F	LYS436

site_id	AF5
Number of Residues	4
Details	binding site for residue SO4 E 706

Chain	Residue
C	PHE156
E	TYR176
E	PHE178
E	SER184

site_id	AF6
Number of Residues	5
Details	binding site for residue 1PE E 707

Chain	Residue
E	TYR103
E	HIS108
E	PHE289
E	LEU321
E	TYR411

site_id	AF7
Number of Residues	6
Details	binding site for residue ZN F 701

Chain	Residue
F	ASP379
F	LYS386
F	ASP459
F	GLU461
F	ZN702
F	TOD703

site_id	AF8
Number of Residues	6
Details	binding site for residue ZN F 702

Chain	Residue
F	LYS374
F	ASP379
F	ASP399
F	GLU461
F	ZN701
F	TOD703

site_id	AF9
Number of Residues	13
Details	binding site for residue TOD F 703

Chain	Residue
F	LYS374
F	ASP379
F	LYS386
F	ASP459
F	GLU461
F	LEU487
F	GLY489
F	ALA490
F	TYR493
F	ZN701
F	ZN702
F	CO3704
F	HOH850

site_id	AG1
Number of Residues	6
Details	binding site for residue CO3 F 704

Chain	Residue
F	ALA460
F	GLU461
F	GLY462
F	ARG463
F	LEU487
F	TOD703

site_id	AG2
Number of Residues	5
Details	binding site for residue ZN G 701

Chain	Residue
G	ASP379
G	ASP459
G	GLU461
G	ZN702
G	TOD703

site_id	AG3
Number of Residues	8
Details	binding site for residue ZN G 702

Chain	Residue
G	LYS374
G	ASP379
G	ASP399
G	GLU461
G	ZN701
G	TOD703
G	CO3704
G	HOH847

site_id	AG4
Number of Residues	13
Details	binding site for residue TOD G 703

Chain	Residue
G	LYS374
G	ASP379
G	LYS386
G	ASP459
G	GLU461
G	LEU487
G	GLY489
G	ILE547
G	ZN701
G	ZN702
G	CO3704
G	HOH847
G	HOH883

site_id	AG5
Number of Residues	7
Details	binding site for residue CO3 G 704

Chain	Residue
G	ALA460
G	GLU461
G	GLY462
G	ARG463
G	LEU487
G	ZN702
G	TOD703

site_id	AG6
Number of Residues	2
Details	binding site for residue SO4 G 705

Chain	Residue
G	HOH818
G	HOH893

site_id	AG7
Number of Residues	5
Details	binding site for residue SO4 G 706

Chain	Residue
A	LYS111
G	GLY126
G	SER220
G	HOH891
J	LYS164

site_id	AG8
Number of Residues	3
Details	binding site for residue 1PE G 707

Chain	Residue
G	ASN104
G	HIS108
G	LYS320

site_id	AG9
Number of Residues	4
Details	binding site for residue 1PE G 708

Chain	Residue
G	TYR103
G	GLU316
G	GLN319
G	LYS320

site_id	AH1
Number of Residues	7
Details	binding site for residue ZN H 701

Chain	Residue
H	LYS374
H	ASP379
H	ASP399
H	GLU461
H	ZN702
H	TOD703
H	HOH840

site_id	AH2
Number of Residues	5
Details	binding site for residue ZN H 702

Chain	Residue
H	ASP379
H	ASP459
H	GLU461
H	ZN701
H	TOD703

site_id	AH3
Number of Residues	12
Details	binding site for residue TOD H 703

Chain	Residue
H	LYS374
H	ASP379
H	LYS386
H	ASP459
H	ALA460
H	GLU461
H	LEU487
H	GLY489
H	ZN701
H	ZN702
H	CO3704
H	HOH840

site_id	AH4
Number of Residues	8
Details	binding site for residue CO3 H 704

Chain	Residue
H	LYS374
H	ASP459
H	ALA460
H	GLU461
H	GLY462
H	ARG463
H	LEU487
H	TOD703

site_id	AH5
Number of Residues	7
Details	binding site for residue 1PE H 705

Chain	Residue
H	TYR103
H	ASN104
H	HIS108
H	PHE289
H	LYS320
H	LEU321
H	TYR411

site_id	AH6
Number of Residues	5
Details	binding site for residue ZN I 701

Chain	Residue
I	ASP379
I	ASP459
I	GLU461
I	ZN702
I	TOD703

site_id	AH7
Number of Residues	8
Details	binding site for residue ZN I 702

Chain	Residue
I	LYS374
I	ASP379
I	ASP399
I	GLU461
I	ZN701
I	TOD703
I	CO3704
I	HOH833

site_id	AH8
Number of Residues	13
Details	binding site for residue TOD I 703

Chain	Residue
I	LYS374
I	ASP379
I	LYS386
I	ASP459
I	GLU461
I	ARG463
I	LEU487
I	GLY489
I	SER554
I	ZN701
I	ZN702
I	CO3704
I	HOH884

site_id	AH9
Number of Residues	8
Details	binding site for residue CO3 I 704

Chain	Residue
I	ASP459
I	ALA460
I	GLU461
I	GLY462
I	ARG463
I	LEU487
I	ZN702
I	TOD703

site_id	AI1
Number of Residues	6
Details	binding site for residue SO4 I 705

Chain	Residue
G	SER435
G	LYS436
H	SER435
H	LYS436
I	SER435
I	LYS436

site_id	AI2
Number of Residues	5
Details	binding site for residue ZN J 701

Chain	Residue
J	ASP379
J	ASP459
J	GLU461
J	ZN702
J	TOD703

site_id	AI3
Number of Residues	6
Details	binding site for residue ZN J 702

Chain	Residue
J	LYS374
J	ASP379
J	ASP399
J	GLU461
J	ZN701
J	TOD703

site_id	AI4
Number of Residues	11
Details	binding site for residue TOD J 703

Chain	Residue
J	LYS374
J	ASP379
J	LYS386
J	ASP459
J	GLU461
J	LEU487
J	THR488
J	GLY489
J	ZN701
J	ZN702
J	CO3704

site_id	AI5
Number of Residues	7
Details	binding site for residue CO3 J 704

Chain	Residue
J	LYS374
J	ALA460
J	GLU461
J	GLY462
J	ARG463
J	LEU487
J	TOD703

site_id	AI6
Number of Residues	5
Details	binding site for residue ZN K 701

Chain	Residue
K	ASP379
K	ASP459
K	GLU461
K	ZN702
K	TOD703

site_id	AI7
Number of Residues	6
Details	binding site for residue ZN K 702

Chain	Residue
K	LYS374
K	ASP379
K	ASP399
K	GLU461
K	ZN701
K	TOD703

site_id	AI8
Number of Residues	13
Details	binding site for residue TOD K 703

Chain	Residue
K	LYS374
K	ASP379
K	LYS386
K	ASP459
K	ALA460
K	GLU461
K	LEU487
K	THR488
K	GLY489
K	TYR493
K	ZN701
K	ZN702
K	CO3704

site_id	AI9
Number of Residues	6
Details	binding site for residue CO3 K 704

Chain	Residue
K	ALA460
K	GLU461
K	GLY462
K	ARG463
K	LEU487
K	TOD703

site_id	AJ1
Number of Residues	5
Details	binding site for residue ZN L 701

Chain	Residue
L	ASP379
L	ASP459
L	GLU461
L	ZN702
L	TOD703

site_id	AJ2
Number of Residues	6
Details	binding site for residue ZN L 702

Chain	Residue
L	LYS374
L	ASP379
L	ASP399
L	GLU461
L	ZN701
L	TOD703

site_id	AJ3
Number of Residues	11
Details	binding site for residue TOD L 703

Chain	Residue
L	LYS374
L	ASP379
L	LYS386
L	ASP459
L	GLU461
L	LEU487
L	THR488
L	GLY489
L	ZN701
L	ZN702
L	CO3704

site_id	AJ4
Number of Residues	7
Details	binding site for residue CO3 L 704

Chain	Residue
L	LYS374
L	ALA460
L	GLU461
L	GLY462
L	ARG463
L	LEU487
L	TOD703

site_id	AJ5
Number of Residues	6
Details	binding site for residue SO4 L 705

Chain	Residue
J	SER435
J	LYS436
K	SER435
K	LYS436
L	SER435
L	LYS436

site_id	AJ6
Number of Residues	10
Details	binding site for Di-peptide LYS G 512 and ASP G 603

Chain	Residue
G	GLU508
G	LEU509
G	ILE510
G	ASN511
G	ILE513
G	LEU514
G	GLN515
G	SER516
G	LEU601
G	ASN602

Functional Information from PROSITE/UniProt

site_id	PS00631
Number of Residues	8
Details	CYTOSOL_AP Cytosol aminopeptidase signature. NTDAEGRL

Chain	Residue	Details
A	ASN457-LEU464

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	204
Details	Region: {"description":"L13 loop","evidences":[{"source":"PubMed","id":"35691342","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

site_id	SWS_FT_FI2
Number of Residues	24
Details	Active site: {"evidences":[{"source":"UniProtKB","id":"P00727","evidenceCode":"ECO:0000250"}]}

Chain

Residue

Details

site_id	SWS_FT_FI3
Number of Residues	36
Details	Binding site: {"evidences":[{"source":"PubMed","id":"20133789","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"21844374","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"23713488","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"25299353","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"25645579","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"35691342","evidenceCode":"ECO:0000269"},{"source":"Reference","evidenceCode":"ECO:0000269","citation":{"citationType":"submission","publicationDate":"JUL-2021","submissionDatabase":"PDB data bank","title":"Structure of M17 with compound.","authors":["Edgar R.","McGowan S.","Webb C.T."]}},{"source":"PDB","id":"3T8W","evidenceCode":"ECO:0000312"},{"source":"PDB","id":"3KQX","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3KQZ","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3KR4","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3KR5","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4K3N","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4R6T","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4R76","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4R7M","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4X2T","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"7RIE","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"7T3V","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

site_id	SWS_FT_FI4
Number of Residues	12
Details	Binding site: {"evidences":[{"source":"PubMed","id":"20133789","evidenceCode":"ECO:0000305"},{"source":"PubMed","id":"23713488","evidenceCode":"ECO:0000305"},{"source":"PDB","id":"3KR5","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4K3N","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

site_id	SWS_FT_FI5
Number of Residues	36
Details	Binding site: {"evidences":[{"source":"PubMed","id":"35691342","evidenceCode":"ECO:0000269"},{"source":"PDB","id":"7SRV","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

site_id	SWS_FT_FI6
Number of Residues	12
Details	Binding site: {"evidences":[{"source":"PubMed","id":"20133789","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"21844374","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"23713488","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"25299353","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"25645579","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"35691342","evidenceCode":"ECO:0000269"},{"source":"Reference","evidenceCode":"ECO:0000269","citation":{"citationType":"submission","publicationDate":"JUL-2021","submissionDatabase":"PDB data bank","title":"Structure of M17 with compound.","authors":["Edgar R.","McGowan S.","Webb C.T."]}},{"source":"PDB","id":"3KQZ","evidenceCode":"ECO:0000312"},{"source":"PDB","id":"3T8W","evidenceCode":"ECO:0000312"},{"source":"PDB","id":"3KR4","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3KR5","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4K3N","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4R6T","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4R76","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4R7M","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4X2T","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"7RIE","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"7T3V","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

site_id	SWS_FT_FI7
Number of Residues	12
Details	Site: {"description":"Essential for hexamer stabilization","evidences":[{"source":"PubMed","id":"35691342","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

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