AMP1_PLAFQ
ID AMP1_PLAFQ Reviewed; 1085 AA.
AC O96935;
DT 21-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2003, sequence version 2.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=M1 family aminopeptidase;
DE EC=3.4.11.-;
DE AltName: Full=Pfa-M1;
OS Plasmodium falciparum (isolate FcB1 / Columbia).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=186763;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=9879894; DOI=10.1016/s0166-6851(98)00143-1;
RA Florent I.C.P., Derhy Z., Allary M., Monsigny M., Mayer R., Schrevel J.;
RT "A Plasmodium falciparum aminopeptidase gene belonging to the M1 family of
RT zinc-metallopeptidases is expressed in erythrocytic stages.";
RL Mol. Biochem. Parasitol. 97:149-160(1998).
RN [2]
RP SEQUENCE REVISION TO N-TERMINUS.
RA Florent I.C.P.;
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, ACTIVITY REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=12166515; DOI=10.1017/s0031182002001828;
RA Allary M., Schrevel J., Florent I.C.P.;
RT "Properties, stage-dependent expression and localization of Plasmodium
RT falciparum M1 family zinc-aminopeptidase.";
RL Parasitology 125:1-10(2002).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 196-1084 IN COMPLEX WITH ZINC
RP IONS AND BESTATIN, CATALYTIC ACTIVITY, FUNCTION, ACTIVITY REGULATION,
RP COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=19196988; DOI=10.1073/pnas.0807398106;
RA McGowan S., Porter C.J., Lowther J., Stack C.M., Golding S.J.,
RA Skinner-Adams T.S., Trenholme K.R., Teuscher F., Donnelly S.M.,
RA Grembecka J., Mucha A., Kafarski P., Degori R., Buckle A.M., Gardiner D.L.,
RA Whisstock J.C., Dalton J.P.;
RT "Structural basis for the inhibition of the essential Plasmodium falciparum
RT M1 neutral aminopeptidase.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:2537-2542(2009).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 195-1085 IN COMPLEX WITH ZINC IONS
RP AND SUBSTRATE ANALOGS, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=21366301; DOI=10.1021/jm101227t;
RA Velmourougane G., Harbut M.B., Dalal S., McGowan S., Oellig C.A.,
RA Meinhardt N., Whisstock J.C., Klemba M., Greenbaum D.C.;
RT "Synthesis of new (-)-bestatin-based inhibitor libraries reveals a novel
RT binding mode in the s1 pocket of the essential malaria m1
RT metalloaminopeptidase.";
RL J. Med. Chem. 54:1655-1666(2011).
CC -!- FUNCTION: Displays aminopeptidase activity with a broad substrate
CC specificity. Preferentially hydrolyzes L-Lys-AMC but also shows strong
CC activity against L-Ala-AMC, L-Arg-AMC and L-Leu-AMC.
CC {ECO:0000269|PubMed:12166515, ECO:0000269|PubMed:19196988}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:19196988, ECO:0000269|PubMed:21366301};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:19196988,
CC ECO:0000269|PubMed:21366301};
CC -!- ACTIVITY REGULATION: Inhibited by 1,10-phenanthroline, EDTA and
CC bestatin. Activity is not affected by phosphoramidin, PMSF, leupeptin,
CC iodoacetamide or pepstatin. {ECO:0000269|PubMed:12166515,
CC ECO:0000269|PubMed:19196988}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.4. Active from pH 5.8 to 8.6, with less than 20% of
CC normal activity at pH 6.0. {ECO:0000269|PubMed:19196988};
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytosol.
CC -!- DEVELOPMENTAL STAGE: Expressed in all erythrocytic stages.
CC {ECO:0000269|PubMed:19196988, ECO:0000269|PubMed:9879894}.
CC -!- PTM: The 120 kDa precursor is cleaved in vitro into 96 kDa and 68 kDa
CC forms.
CC -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
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DR EMBL; Y09081; CAA70301.2; -; Genomic_DNA.
DR PIR; T28636; T28636.
DR PDB; 3EBG; X-ray; 2.10 A; A=196-1084.
DR PDB; 3EBH; X-ray; 1.65 A; A=196-1084.
DR PDB; 3EBI; X-ray; 2.00 A; A=195-1084.
DR PDB; 3Q43; X-ray; 1.80 A; A=195-1085.
DR PDB; 3Q44; X-ray; 1.80 A; A=195-1085.
DR PDB; 3T8V; X-ray; 1.80 A; A=196-1084.
DR PDB; 4J3B; X-ray; 2.20 A; A=197-1085.
DR PDB; 4K5L; X-ray; 1.91 A; A=195-1085.
DR PDB; 4K5M; X-ray; 1.75 A; A=195-1085.
DR PDB; 4K5N; X-ray; 1.91 A; A=196-1084.
DR PDB; 4K5O; X-ray; 1.90 A; A=196-1084.
DR PDB; 4K5P; X-ray; 1.85 A; A=196-1084.
DR PDB; 4R5T; X-ray; 1.98 A; A=196-1084.
DR PDB; 4R5V; X-ray; 2.10 A; A=196-1084.
DR PDB; 4R5X; X-ray; 1.85 A; A=182-1084.
DR PDB; 4X2U; X-ray; 1.60 A; A=196-1084.
DR PDB; 4ZW3; X-ray; 1.80 A; A=195-1084.
DR PDB; 4ZW5; X-ray; 1.80 A; A=195-1084.
DR PDB; 4ZW6; X-ray; 1.90 A; A=195-1084.
DR PDB; 4ZW7; X-ray; 1.95 A; A=195-1084.
DR PDB; 4ZW8; X-ray; 2.00 A; A=195-1084.
DR PDB; 4ZX3; X-ray; 2.00 A; A=195-1084.
DR PDB; 4ZX4; X-ray; 1.90 A; A=195-1084.
DR PDB; 4ZX5; X-ray; 1.95 A; A=195-1084.
DR PDB; 4ZX6; X-ray; 2.05 A; A=195-1084.
DR PDB; 5XM7; X-ray; 1.96 A; A=195-1085.
DR PDB; 5Y19; X-ray; 1.83 A; A=195-1085.
DR PDB; 5Y1H; X-ray; 1.73 A; A=195-1085.
DR PDB; 5Y1K; X-ray; 1.81 A; A=195-1085.
DR PDB; 5Y1Q; X-ray; 2.14 A; A=195-1085.
DR PDB; 5Y1R; X-ray; 1.69 A; A=195-1085.
DR PDB; 5Y1S; X-ray; 1.66 A; A=195-1085.
DR PDB; 5Y1T; X-ray; 2.14 A; A=195-1085.
DR PDB; 5Y1V; X-ray; 1.62 A; A=195-1085.
DR PDB; 5Y1W; X-ray; 1.56 A; A=195-1085.
DR PDB; 5Y1X; X-ray; 1.55 A; A=195-1085.
DR PDB; 5Y3I; X-ray; 1.73 A; A=195-1085.
DR PDB; 6EA1; X-ray; 1.81 A; A=196-1084.
DR PDB; 6EA2; X-ray; 1.35 A; A=196-1084.
DR PDB; 6EAA; X-ray; 1.65 A; A=196-1084.
DR PDB; 6EAB; X-ray; 1.85 A; A=196-1084.
DR PDB; 6EE3; X-ray; 1.82 A; A=196-1084.
DR PDB; 6EE4; X-ray; 1.58 A; A=196-1084.
DR PDB; 6EE6; X-ray; 1.50 A; A=196-1084.
DR PDB; 6EED; X-ray; 1.50 A; A=196-1084.
DR PDBsum; 3EBG; -.
DR PDBsum; 3EBH; -.
DR PDBsum; 3EBI; -.
DR PDBsum; 3Q43; -.
DR PDBsum; 3Q44; -.
DR PDBsum; 3T8V; -.
DR PDBsum; 4J3B; -.
DR PDBsum; 4K5L; -.
DR PDBsum; 4K5M; -.
DR PDBsum; 4K5N; -.
DR PDBsum; 4K5O; -.
DR PDBsum; 4K5P; -.
DR PDBsum; 4R5T; -.
DR PDBsum; 4R5V; -.
DR PDBsum; 4R5X; -.
DR PDBsum; 4X2U; -.
DR PDBsum; 4ZW3; -.
DR PDBsum; 4ZW5; -.
DR PDBsum; 4ZW6; -.
DR PDBsum; 4ZW7; -.
DR PDBsum; 4ZW8; -.
DR PDBsum; 4ZX3; -.
DR PDBsum; 4ZX4; -.
DR PDBsum; 4ZX5; -.
DR PDBsum; 4ZX6; -.
DR PDBsum; 5XM7; -.
DR PDBsum; 5Y19; -.
DR PDBsum; 5Y1H; -.
DR PDBsum; 5Y1K; -.
DR PDBsum; 5Y1Q; -.
DR PDBsum; 5Y1R; -.
DR PDBsum; 5Y1S; -.
DR PDBsum; 5Y1T; -.
DR PDBsum; 5Y1V; -.
DR PDBsum; 5Y1W; -.
DR PDBsum; 5Y1X; -.
DR PDBsum; 5Y3I; -.
DR PDBsum; 6EA1; -.
DR PDBsum; 6EA2; -.
DR PDBsum; 6EAA; -.
DR PDBsum; 6EAB; -.
DR PDBsum; 6EE3; -.
DR PDBsum; 6EE4; -.
DR PDBsum; 6EE6; -.
DR PDBsum; 6EED; -.
DR AlphaFoldDB; O96935; -.
DR SMR; O96935; -.
DR BindingDB; O96935; -.
DR ChEMBL; CHEMBL4117; -.
DR DrugCentral; O96935; -.
DR MEROPS; M01.029; -.
DR PRIDE; O96935; -.
DR BRENDA; 3.4.11.20; 4889.
DR EvolutionaryTrace; O96935; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0004177; F:aminopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008237; F:metallopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR Gene3D; 1.10.390.10; -; 1.
DR Gene3D; 1.25.50.10; -; 1.
DR Gene3D; 2.60.40.1730; -; 1.
DR Gene3D; 2.60.40.1840; -; 1.
DR InterPro; IPR045357; Aminopeptidase_N-like_N.
DR InterPro; IPR042097; Aminopeptidase_N-like_N_sf.
DR InterPro; IPR038438; PepN_Ig-like_sf.
DR InterPro; IPR001930; Peptidase_M1.
DR InterPro; IPR014782; Peptidase_M1_dom.
DR InterPro; IPR012779; Peptidase_M1_pepN.
DR InterPro; IPR024601; Peptidase_M1_pepN_C.
DR InterPro; IPR037144; Peptidase_M1_pepN_C_sf.
DR InterPro; IPR035414; Peptidase_M1_pepN_Ig-like.
DR InterPro; IPR027268; Peptidase_M4/M1_CTD_sf.
DR PANTHER; PTHR46322; PTHR46322; 1.
DR Pfam; PF11940; DUF3458; 1.
DR Pfam; PF17432; DUF3458_C; 1.
DR Pfam; PF01433; Peptidase_M1; 1.
DR Pfam; PF17900; Peptidase_M1_N; 1.
DR PRINTS; PR00756; ALADIPTASE.
DR SUPFAM; SSF63737; SSF63737; 1.
DR TIGRFAMs; TIGR02414; pepN_proteo; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aminopeptidase; Cytoplasm; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Zinc.
FT CHAIN 1..1085
FT /note="M1 family aminopeptidase"
FT /id="PRO_0000095100"
FT REGION 108..130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 111..130
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 497
FT /note="Proton acceptor"
FT /evidence="ECO:0000305"
FT BINDING 319
FT /ligand="substrate"
FT BINDING 460..464
FT /ligand="substrate"
FT BINDING 496
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 500
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT BINDING 519
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT SITE 580
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000305"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 208..220
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 225..235
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 244..247
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 252..258
FT /evidence="ECO:0007829|PDB:6EA2"
FT TURN 266..268
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 269..271
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 273..278
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 280..282
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 288..296
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 298..300
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 306..310
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 313..317
FT /evidence="ECO:0007829|PDB:6EA2"
FT TURN 319..322
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 323..325
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 337..346
FT /evidence="ECO:0007829|PDB:6EA2"
FT TURN 347..349
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 352..365
FT /evidence="ECO:0007829|PDB:6EA2"
FT TURN 366..368
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 369..380
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 382..384
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 387..390
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 392..400
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 402..404
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 407..415
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 416..421
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 423..440
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 446..455
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 458..462
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 467..471
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 472..474
FT /evidence="ECO:0007829|PDB:6EA2"
FT TURN 479..481
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 485..499
FT /evidence="ECO:0007829|PDB:6EA2"
FT TURN 500..502
FT /evidence="ECO:0007829|PDB:6EA2"
FT TURN 504..506
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 507..511
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 512..514
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 515..534
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 538..555
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 566..569
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 571..573
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 577..610
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 613..615
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 617..632
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 641..643
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 644..647
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 653..661
FT /evidence="ECO:0007829|PDB:6EA2"
FT TURN 662..665
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 666..674
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 689..696
FT /evidence="ECO:0007829|PDB:6EA2"
FT TURN 698..700
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 708..712
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 714..722
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 729..733
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 738..743
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 748..757
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 761..788
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 801..811
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 818..824
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 830..833
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 834..836
FT /evidence="ECO:0007829|PDB:6EA2"
FT STRAND 838..840
FT /evidence="ECO:0007829|PDB:5Y1X"
FT HELIX 842..870
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 872..875
FT /evidence="ECO:0007829|PDB:6EA2"
FT TURN 879..882
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 889..907
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 913..920
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 926..935
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 936..938
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 942..953
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 957..968
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 975..985
FT /evidence="ECO:0007829|PDB:6EA2"
FT TURN 986..989
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 993..1004
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 1007..1010
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 1016..1029
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 1033..1039
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 1040..1048
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 1051..1065
FT /evidence="ECO:0007829|PDB:6EA2"
FT HELIX 1072..1081
FT /evidence="ECO:0007829|PDB:6EA2"
SQ SEQUENCE 1085 AA; 126062 MW; 72AE30928D6BD550 CRC64;
MKLTKGCAYK YIIFTVLILA NILYDNKKRC MIKKNLRISS CGIISRLLKS NSNYNSFNKN
YNFTSAISEL QFSNFWNLDI LQKDIFSNIH NNKNKPQSYI IHKRLMSEKG DNNNNNHQNN
NGNDNKKRLG SVVNNEENTC SDKRMKPFEE GHGITQVDKM NNNSDHLQQN GVMNLNSNNV
ENNNNNNSVV VKKNEPKIHY RKDYKPSGFI INNVTLNINI HDNETIVRSV LDMDISKHNV
GEDLVFDGVG LKINEISINN KKLVEGEEYT YDNEFLTIFS KFVPKSKFAF SSEVIIHPET
NYALTGLYKS KNIIVSQCEA TGFRRITFFI DRPDMMAKYD VTVTADKEKY PVLLSNGDKV
NEFEIPGGRH GARFNDPHLK PCYLFAVVAG DLKHLSATYI TKYTKKKVEL YVFSEEKYVS
KLQWALECLK KSMAFDEDYF GLEYDLSRLN LVAVSDFNVG AMENKGLNIF NANSLLASKK
NSIDFSYARI LTVVGHEYFH NYTGNRVTLR DWFQLTLKEG LTVHRENLFS EEMTKTVTTR
LSHVDLLRSV QFLEDSSPLS HPIRPESYVS MENFYTTTVY DKGSEVMRMY LTILGEEYYK
KGFDIYIKKN DGNTATCEDF NYAMEQAYKM KKADNSANLN QYLLWFSQSG TPHVSFKYNY
DAEKKQYSIH VNQYTKPDEN QKEKKPLFIP ISVGLINPEN GKEMISQTTL ELTKESDTFV
FNNIAVKPIP SLFRGFSAPV YIEDNLTDEE RILLLKYDSD AFVRYNSCTN IYMKQILMNY
NEFLKAKNEK LESFNLTPVN AQFIDAIKYL LEDPHADAGF KSYIVSLPQD RYIINFVSNL
DTDVLADTKE YIYKQIGDKL NDVYYKMFKS LEAKADDLTY FNDESHVDFD QMNMRTLRNT
LLSLLSKAQY PNILNEIIEH SKSPYPSNWL TSLSVSAYFD KYFELYDKTY KLSKDDELLL
QEWLKTVSRS DRKDIYEILK KLENEVLKDS KNPNDIRAVY LPFTNNLRRF HDISGKGYKL
IAEVITKTDK FNPMVATQLC EPFKLWNKLD TKRQELMLNE MNTMLQEPNI SNNLKEYLLR
LTNKL
