BAPA_SPHXN
ID BAPA_SPHXN Reviewed; 402 AA.
AC Q52VH2;
DT 29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Beta-peptidyl aminopeptidase BapA {ECO:0000303|PubMed:16109932};
DE EC=3.4.11.25 {ECO:0000269|PubMed:16109932, ECO:0000269|PubMed:17064315, ECO:0000269|PubMed:22961926, ECO:0000269|PubMed:22980995};
DE Contains:
DE RecName: Full=Beta-peptidyl aminopeptidase BapA alpha subunit {ECO:0000303|PubMed:16109932};
DE Contains:
DE RecName: Full=Beta-peptidyl aminopeptidase BapA beta subunit {ECO:0000303|PubMed:16109932};
DE Flags: Precursor;
GN Name=bapA {ECO:0000303|PubMed:16109932};
OS Sphingosinicella xenopeptidilytica.
OC Bacteria; Proteobacteria; Alphaproteobacteria; Sphingomonadales;
OC Sphingosinicellaceae; Sphingosinicella.
OX NCBI_TaxID=364098 {ECO:0000312|EMBL:AAX93858.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 30-49 AND 279-291,
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND SUBCELLULAR LOCATION.
RC STRAIN=DSM 17130 / CCUG 52537 / 3-2W4 {ECO:0000312|EMBL:AAX93858.1};
RX PubMed=16109932; DOI=10.1128/jb.187.17.5910-5917.2005;
RA Geueke B., Namoto K., Seebach D., Kohler H.P.;
RT "A novel beta-peptidyl aminopeptidase (BapA) from strain 3-2W4 cleaves
RT peptide bonds of synthetic beta-tri- and beta-dipeptides.";
RL J. Bacteriol. 187:5910-5917(2005).
RN [2]
RP CATALYTIC ACTIVITY, FUNCTION, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=17064315; DOI=10.1111/j.1742-4658.2006.05519.x;
RA Geueke B., Heck T., Limbach M., Nesatyy V., Seebach D., Kohler H.P.;
RT "Bacterial beta-peptidyl aminopeptidases with unique substrate
RT specificities for beta-oligopeptides and mixed beta,alpha-oligopeptides.";
RL FEBS J. 273:5261-5272(2006).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS), X-RAY CRYSTALLOGRAPHY (1.80
RP ANGSTROMS) IN COMPLEX WITH INHIBITOR AEBSF, CATALYTIC ACTIVITY, ACTIVE
RP SITE, AUTOPROTEOLYTIC PROCESSING, SUBUNIT, AND MUTAGENESIS OF GLU-162;
RP LYS-277; ASN-278; SER-279; SER-317 AND GLU-319.
RX PubMed=22980995; DOI=10.1016/j.str.2012.07.017;
RA Merz T., Heck T., Geueke B., Mittl P.R., Briand C., Seebach D.,
RA Kohler H.P., Gruetter M.G.;
RT "Autoproteolytic and catalytic mechanisms for the beta-aminopeptidase
RT BapA--a member of the Ntn hydrolase family.";
RL Structure 20:1850-1860(2012).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS)IN COMPLEX WITH INHIBITOR AMPICILLIN,
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH INHIBITOR AMP(HYD),
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBUNIT.
RX PubMed=22961926; DOI=10.1002/cbic.201200393;
RA Heck T., Merz T., Reimer A., Seebach D., Rentsch D., Briand C.,
RA Gruetter M.G., Kohler H.P., Geueke B.;
RT "Crystal structures of BapA complexes with beta-lactam-derived inhibitors
RT illustrate substrate specificity and enantioselectivity of beta-
RT aminopeptidases.";
RL ChemBioChem 13:2137-2145(2012).
CC -!- FUNCTION: Beta-aminopeptidase that can cleave synthetic beta-peptides
CC which consist of backbone-elongated beta-amino acid residues that are
CC not processed by common proteolytic enzymes. Can cleave the beta-
CC peptides beta-homoVal-beta-homoAla-beta-homoLeu and beta-homoAla-beta-
CC homoLeu. Requires a beta-amino acid at the N-terminus of peptide
CC substrates and cleaves the peptide bond between the N-terminal beta-
CC amino acid and the amino acid at the second position of tripeptidic
CC substrates of the general structure H-betahXaa-Ile-betahTyr-OH
CC according to the following preferences with regard to the side chain of
CC the N-terminal beta-amino acid: aliphatic and aromatic > OH-containing
CC > hydrogen, basic and polar. {ECO:0000269|PubMed:16109932,
CC ECO:0000269|PubMed:17064315}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleaves N-terminal beta-homoamino acids from peptides composed
CC of 2 to 6 amino acids.; EC=3.4.11.25;
CC Evidence={ECO:0000269|PubMed:16109932, ECO:0000269|PubMed:17064315,
CC ECO:0000269|PubMed:22961926, ECO:0000269|PubMed:22980995};
CC -!- ACTIVITY REGULATION: Inhibited by AEBSF (4-(2-
CC aminoethyl)benzenesulfonyl fluoride, Pefabloc SC), ampicillin and
CC AMP(hyd) (ampillicin-derived penicilloic acid).
CC {ECO:0000269|PubMed:17064315, ECO:0000269|PubMed:22961926,
CC ECO:0000269|PubMed:22980995}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9.0 mM for beta-homoVal-beta-homoAla-beta-homoLeu
CC {ECO:0000269|PubMed:17064315};
CC KM=20 mM for beta-homoAla-beta-homoLeu {ECO:0000269|PubMed:17064315};
CC KM=8.2 mM for beta-homoGly-pNA {ECO:0000269|PubMed:17064315};
CC KM=1.2 mM for beta-homoAla-pNA {ECO:0000269|PubMed:22961926};
CC Vmax=3.1 umol/min/mg enzyme with beta-homoVal-beta-homoAla-beta-
CC homoLeu as substrate {ECO:0000269|PubMed:17064315};
CC Vmax=1.1 umol/min/mg enzyme with beta-homoAla-beta-homoLeu as
CC substrate {ECO:0000269|PubMed:17064315};
CC Vmax=0.026 umol/min/mg enzyme with carnosine as substrate
CC {ECO:0000269|PubMed:17064315};
CC Vmax=0.98 umol/min/mg enzyme with beta-homoVal-Ile-beta-homoTyr as
CC substrate {ECO:0000269|PubMed:17064315};
CC Vmax=1.9 umol/min/mg enzyme with beta-homoVal-Ile-beta-homoTyr as
CC substrate {ECO:0000269|PubMed:17064315};
CC Vmax=0.68 umol/min/mg enzyme with beta-homoPhe-Ile-beta-homoTyr as
CC substrate {ECO:0000269|PubMed:17064315};
CC Vmax=0.47 umol/min/mg enzyme with beta-homoTyr-Ile-beta-homoTyr as
CC substrate {ECO:0000269|PubMed:17064315};
CC Vmax=0.047 umol/min/mg enzyme with beta-homoTrp-Ile-beta-homoTyr as
CC substrate {ECO:0000269|PubMed:17064315};
CC Vmax=0.095 umol/min/mg enzyme with beta-homoSer-Ile-beta-homoTyr as
CC substrate {ECO:0000269|PubMed:17064315};
CC Vmax=0.068 umol/min/mg enzyme with beta-homoThr-Ile-beta-homoTyr as
CC substrate {ECO:0000269|PubMed:17064315};
CC Vmax=0.017 umol/min/mg enzyme with beta-homoLys-Ile-beta-homoTyr as
CC substrate {ECO:0000269|PubMed:17064315};
CC Vmax=0.028 umol/min/mg enzyme with D-beta-homoVal-Ile-beta-homoTyr as
CC substrate {ECO:0000269|PubMed:17064315};
CC Vmax=16.4 umol/min/mg enzyme with beta-homoAla-pNA as substrate
CC {ECO:0000269|PubMed:22961926};
CC pH dependence:
CC Optimum pH is between 8 and 9. {ECO:0000269|PubMed:17064315};
CC -!- SUBUNIT: Heterooctamer of 4 heterodimers ((alpha:beta)4); each
CC heterodimer is composed of an alpha subunit and a beta subunit
CC processed from the same precursor. {ECO:0000269|PubMed:16109932,
CC ECO:0000269|PubMed:22961926, ECO:0000269|PubMed:22980995}.
CC -!- INTERACTION:
CC Q52VH2; Q52VH2: bapA; NbExp=2; IntAct=EBI-16013301, EBI-16013301;
CC -!- SUBCELLULAR LOCATION: Periplasm {ECO:0000303|PubMed:16109932}.
CC -!- PTM: Autoproteolytic processing to generate the alpha and beta subunit
CC is required for self-activation and is proposed to use a similar
CC mechanism as substrate cleavage. {ECO:0000303|PubMed:22980995}.
CC -!- SIMILARITY: Belongs to the peptidase S58 family. {ECO:0000305}.
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DR EMBL; AY897555; AAX93858.1; -; Genomic_DNA.
DR PDB; 3N2W; X-ray; 1.45 A; A/B/C/D=30-402.
DR PDB; 3N33; X-ray; 1.80 A; A/B/C/D=30-402.
DR PDB; 3N5I; X-ray; 1.80 A; A/B/C/D=30-402.
DR PDB; 3NDV; X-ray; 1.70 A; A/B/C/D=30-402.
DR PDB; 3NFB; X-ray; 1.85 A; A/B/C/D=30-402.
DR PDBsum; 3N2W; -.
DR PDBsum; 3N33; -.
DR PDBsum; 3N5I; -.
DR PDBsum; 3NDV; -.
DR PDBsum; 3NFB; -.
DR AlphaFoldDB; Q52VH2; -.
DR SMR; Q52VH2; -.
DR DIP; DIP-59978N; -.
DR MEROPS; P01.002; -.
DR KEGG; ag:AAX93858; -.
DR BioCyc; MetaCyc:MON-16515; -.
DR BRENDA; 3.4.11.25; 12099.
DR GO; GO:0042597; C:periplasmic space; IEA:UniProtKB-SubCell.
DR GO; GO:0004177; F:aminopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR016117; ArgJ-like_dom_sf.
DR InterPro; IPR005321; Peptidase_S58_DmpA.
DR PANTHER; PTHR36512; PTHR36512; 1.
DR Pfam; PF03576; Peptidase_S58; 1.
DR SUPFAM; SSF56266; SSF56266; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aminopeptidase; Direct protein sequencing; Hydrolase;
KW Periplasm; Protease; Signal.
FT SIGNAL 1..29
FT /evidence="ECO:0000269|PubMed:16109932"
FT CHAIN 30..278
FT /note="Beta-peptidyl aminopeptidase BapA alpha subunit"
FT /evidence="ECO:0000303|PubMed:16109932"
FT /id="PRO_0000430763"
FT CHAIN 279..402
FT /note="Beta-peptidyl aminopeptidase BapA beta subunit"
FT /evidence="ECO:0000303|PubMed:16109932"
FT /id="PRO_0000430764"
FT ACT_SITE 279
FT /note="Nucleophile"
FT /evidence="ECO:0000303|PubMed:22980995"
FT ACT_SITE 317
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000303|PubMed:22980995"
FT ACT_SITE 319
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000303|PubMed:22980995"
FT MUTAGEN 162
FT /note="E->A: Delays precursor cleavage and abolishes
FT enzymatic activity."
FT /evidence="ECO:0000269|PubMed:22980995"
FT MUTAGEN 277
FT /note="K->A: Delays precursor cleavage."
FT /evidence="ECO:0000269|PubMed:22980995"
FT MUTAGEN 278
FT /note="N->A: Delays precursor cleavage."
FT /evidence="ECO:0000269|PubMed:22980995"
FT MUTAGEN 279
FT /note="S->A: Abolishes precursor cleavage and enzymatic
FT activity."
FT /evidence="ECO:0000269|PubMed:22980995"
FT MUTAGEN 317
FT /note="S->A: Abolishes precursor cleavage and enzymatic
FT activity."
FT /evidence="ECO:0000269|PubMed:22980995"
FT MUTAGEN 319
FT /note="E->A: Abolishes precursor cleavage and reduces
FT enzymatic activity."
FT /evidence="ECO:0000269|PubMed:22980995"
FT HELIX 33..36
FT /evidence="ECO:0007829|PDB:3N2W"
FT STRAND 46..49
FT /evidence="ECO:0007829|PDB:3N2W"
FT HELIX 50..52
FT /evidence="ECO:0007829|PDB:3N2W"
FT STRAND 57..65
FT /evidence="ECO:0007829|PDB:3N2W"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:3N5I"
FT STRAND 77..85
FT /evidence="ECO:0007829|PDB:3N2W"
FT STRAND 94..103
FT /evidence="ECO:0007829|PDB:3N2W"
FT HELIX 111..117
FT /evidence="ECO:0007829|PDB:3N2W"
FT STRAND 118..122
FT /evidence="ECO:0007829|PDB:3N2W"
FT STRAND 124..128
FT /evidence="ECO:0007829|PDB:3N2W"
FT HELIX 129..131
FT /evidence="ECO:0007829|PDB:3N2W"
FT HELIX 132..146
FT /evidence="ECO:0007829|PDB:3N2W"
FT HELIX 149..155
FT /evidence="ECO:0007829|PDB:3N2W"
FT STRAND 159..163
FT /evidence="ECO:0007829|PDB:3N2W"
FT TURN 166..168
FT /evidence="ECO:0007829|PDB:3N2W"
FT HELIX 178..187
FT /evidence="ECO:0007829|PDB:3N2W"
FT STRAND 189..192
FT /evidence="ECO:0007829|PDB:3N2W"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:3N2W"
FT STRAND 212..222
FT /evidence="ECO:0007829|PDB:3N2W"
FT STRAND 225..235
FT /evidence="ECO:0007829|PDB:3N2W"
FT TURN 240..242
FT /evidence="ECO:0007829|PDB:3N2W"
FT TURN 251..253
FT /evidence="ECO:0007829|PDB:3N2W"
FT TURN 269..272
FT /evidence="ECO:0007829|PDB:3N2W"
FT STRAND 280..286
FT /evidence="ECO:0007829|PDB:3N2W"
FT HELIX 292..300
FT /evidence="ECO:0007829|PDB:3N2W"
FT HELIX 302..308
FT /evidence="ECO:0007829|PDB:3N2W"
FT STRAND 319..330
FT /evidence="ECO:0007829|PDB:3N2W"
FT HELIX 347..371
FT /evidence="ECO:0007829|PDB:3N2W"
FT HELIX 378..380
FT /evidence="ECO:0007829|PDB:3NFB"
FT STRAND 381..383
FT /evidence="ECO:0007829|PDB:3N2W"
FT HELIX 388..398
FT /evidence="ECO:0007829|PDB:3N2W"
SQ SEQUENCE 402 AA; 41531 MW; 83A755254EA30436 CRC64;
MTSTQRLWSG ALPLLTALIV SIAATASLAG PRARDLGVPF EGTPGALNAI TDVAGVEVGH
TTVISGDGAM VIGKGPYRTG VTIIHPLGKT SLDGVAAGRA VINGTGEWTG MHLVDEVGQF
LGPIALTGTG NVGLVHQSMM DWSVGKVPEE ALFSRLLPVV AETLDNRLND VFGHGLTRDH
VFAALDGAKG GPVAEGNVGG GTGMIAYTFK GGIGTSSRVV SAGDTRYTVG VLVQANHGDR
NDLRIAGVQI GKEIKGAWPE VNGIVAAGPD AGKPQDKNSL LIVIATDAPL MPHQLERMAR
RAALGVGRNG STAGALSGEF ALAFSTSHVI PLGGKPRLPA IINDTDSETM NALFRGVVQA
TEEALVNQLV ASETMTGANN AKVYGIPHDQ LARIMKARFP RR
