PBPA_MYCTU
ID PBPA_MYCTU Reviewed; 491 AA.
AC P9WKD1; L0T427; P71586; Q7DAK5;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=Peptidoglycan D,D-transpeptidase PbpA {ECO:0000305};
DE EC=3.4.16.4 {ECO:0000305|PubMed:29530985};
DE AltName: Full=Penicillin-binding protein A {ECO:0000303|PubMed:20206184};
DE Short=PBPA {ECO:0000303|PubMed:20206184};
GN Name=pbpA; OrderedLocusNames=Rv0016c; ORFNames=MTCY10H4.16c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP RETRACTED PAPER.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16436437; DOI=10.1099/mic.0.28630-0;
RA Dasgupta A., Datta P., Kundu M., Basu J.;
RT "The serine/threonine kinase PknB of Mycobacterium tuberculosis
RT phosphorylates PBPA, a penicillin-binding protein required for cell
RT division.";
RL Microbiology 152:493-504(2006).
RN [3]
RP RETRACTION NOTICE OF PUBMED:16436437.
RX PubMed=26231854; DOI=10.1099/mic.0.000110;
RA Dasgupta A., Datta P., Kundu M., Basu J.;
RL Microbiology 161:1537-1537(2015).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF SER-281 AND LYS-424.
RX PubMed=29530985; DOI=10.1074/jbc.m117.811190;
RA Arora D., Chawla Y., Malakar B., Singh A., Nandicoori V.K.;
RT "The transpeptidase PbpA and noncanonical transglycosylase RodA of
RT Mycobacterium tuberculosis play important roles in regulating bacterial
RT cell lengths.";
RL J. Biol. Chem. 293:6497-6516(2018).
RN [6] {ECO:0007744|PDB:3LO7}
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 35-491, AND DISULFIDE BOND.
RC STRAIN=H37Rv;
RX PubMed=20206184; DOI=10.1016/j.jmb.2010.02.046;
RA Fedarovich A., Nicholas R.A., Davies C.;
RT "Unusual conformation of the SxN motif in the crystal structure of
RT penicillin-binding protein A from Mycobacterium tuberculosis.";
RL J. Mol. Biol. 398:54-65(2010).
RN [7] {ECO:0007744|PDB:3UN7, ECO:0007744|PDB:3UPN, ECO:0007744|PDB:3UPO, ECO:0007744|PDB:3UPP}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 35-491 OF APOENZYME AND IN
RP COMPLEXES WITH ANTIBIOTICS, ACTIVITY REGULATION, DOMAIN, AND DISULFIDE
RP BOND.
RX PubMed=22365933; DOI=10.1016/j.jmb.2012.02.021;
RA Fedarovich A., Nicholas R.A., Davies C.;
RT "The role of the beta5-alpha11 loop in the active-site dynamics of acylated
RT penicillin-binding protein A from Mycobacterium tuberculosis.";
RL J. Mol. Biol. 418:316-330(2012).
CC -!- FUNCTION: Transpeptidase that catalyzes cross-linking of the
CC peptidoglycan cell wall (Probable). Required for the regulation of cell
CC length. Plays critical roles for the survival of the pathogen inside
CC the host. Required for both bacterial survival and formation of
CC granuloma structures in a guinea pig infection model (PubMed:29530985).
CC {ECO:0000269|PubMed:29530985, ECO:0000305|PubMed:29530985}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Preferential cleavage: (Ac)2-L-Lys-D-Ala-|-D-Ala. Also
CC transpeptidation of peptidyl-alanyl moieties that are N-acyl
CC substituents of D-alanine.; EC=3.4.16.4;
CC Evidence={ECO:0000305|PubMed:29530985};
CC -!- ACTIVITY REGULATION: Inhibited by the antibiotics imipenem, penicillin
CC G, and ceftriaxone. {ECO:0000269|PubMed:22365933}.
CC -!- PATHWAY: Cell wall biogenesis; peptidoglycan biosynthesis.
CC {ECO:0000305|PubMed:29530985}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000305}; Single-pass
CC type II membrane protein {ECO:0000255}.
CC -!- DOMAIN: The apo form can adopt multiple conformations
CC (PubMed:22365933). The beta5-alpha11 loop near the active site is a
CC flexible region that can adopt a variety of conformations in the
CC acylated state of PBPA and appears important for acylation
CC (PubMed:22365933). {ECO:0000269|PubMed:22365933}.
CC -!- DISRUPTION PHENOTYPE: Deletion of the gene does not impact in vitro
CC growth, but it leads to aberrations in the cell length. Deletion mutant
CC shows much higher sensitivity to oxacillin and clavulanic acid. Mutant
CC shows compromised bacterial virulence in the host.
CC {ECO:0000269|PubMed:29530985}.
CC -!- SIMILARITY: Belongs to the transpeptidase family. {ECO:0000305}.
CC -!- CAUTION: An article reported the phosphorylation of PbpA by PknB, but
CC this paper was later retracted as some figures were modified prior to
CC publication. {ECO:0000305|PubMed:16436437,
CC ECO:0000305|PubMed:26231854}.
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DR EMBL; AL123456; CCP42738.1; -; Genomic_DNA.
DR PIR; F70699; F70699.
DR RefSeq; NP_214530.1; NC_000962.3.
DR RefSeq; WP_003899775.1; NZ_NVQJ01000005.1.
DR PDB; 3LO7; X-ray; 2.05 A; A/B=35-491.
DR PDB; 3UN7; X-ray; 2.00 A; A/B=35-491.
DR PDB; 3UPN; X-ray; 2.20 A; A/B=35-491.
DR PDB; 3UPO; X-ray; 2.30 A; A/B=35-491.
DR PDB; 3UPP; X-ray; 2.40 A; A/B=35-491.
DR PDBsum; 3LO7; -.
DR PDBsum; 3UN7; -.
DR PDBsum; 3UPN; -.
DR PDBsum; 3UPO; -.
DR PDBsum; 3UPP; -.
DR AlphaFoldDB; P9WKD1; -.
DR SMR; P9WKD1; -.
DR IntAct; P9WKD1; 1.
DR STRING; 83332.Rv0016c; -.
DR iPTMnet; P9WKD1; -.
DR PaxDb; P9WKD1; -.
DR DNASU; 887078; -.
DR GeneID; 45423975; -.
DR GeneID; 887078; -.
DR KEGG; mtu:Rv0016c; -.
DR TubercuList; Rv0016c; -.
DR eggNOG; COG0768; Bacteria.
DR OMA; MWAPVTG; -.
DR PhylomeDB; P9WKD1; -.
DR UniPathway; UPA00219; -.
DR PHI-base; PHI:7983; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0008658; F:penicillin binding; IBA:GO_Central.
DR GO; GO:0071972; F:peptidoglycan L,D-transpeptidase activity; IBA:GO_Central.
DR GO; GO:0009002; F:serine-type D-Ala-D-Ala carboxypeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0071555; P:cell wall organization; IBA:GO_Central.
DR GO; GO:0009252; P:peptidoglycan biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR Gene3D; 3.40.710.10; -; 1.
DR InterPro; IPR012338; Beta-lactam/transpept-like.
DR InterPro; IPR001460; PCN-bd_Tpept.
DR Pfam; PF00905; Transpeptidase; 1.
DR SUPFAM; SSF56601; SSF56601; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell inner membrane; Cell membrane; Cell shape;
KW Cell wall biogenesis/degradation; Disulfide bond; Hydrolase; Membrane;
KW Peptidoglycan synthesis; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..491
FT /note="Peptidoglycan D,D-transpeptidase PbpA"
FT /id="PRO_0000343832"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 8..28
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 29..491
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT REGION 160..484
FT /note="Transpeptidase"
FT ACT_SITE 222
FT /note="Acyl-ester intermediate"
FT /evidence="ECO:0000250|UniProtKB:P0AD65"
FT DISULFID 266..282
FT /evidence="ECO:0000269|PubMed:20206184,
FT ECO:0000269|PubMed:22365933"
FT MUTAGEN 281
FT /note="S->A: Can rescue the deletion mutant."
FT /evidence="ECO:0000269|PubMed:29530985"
FT MUTAGEN 424
FT /note="K->G: Cannot rescue the deletion mutant."
FT /evidence="ECO:0000269|PubMed:29530985"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:3LO7"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:3UN7"
FT STRAND 60..67
FT /evidence="ECO:0007829|PDB:3UN7"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:3UN7"
FT STRAND 74..77
FT /evidence="ECO:0007829|PDB:3UN7"
FT HELIX 81..88
FT /evidence="ECO:0007829|PDB:3UN7"
FT TURN 93..95
FT /evidence="ECO:0007829|PDB:3UN7"
FT HELIX 99..103
FT /evidence="ECO:0007829|PDB:3UN7"
FT HELIX 105..108
FT /evidence="ECO:0007829|PDB:3UN7"
FT TURN 113..115
FT /evidence="ECO:0007829|PDB:3UN7"
FT HELIX 116..125
FT /evidence="ECO:0007829|PDB:3UN7"
FT STRAND 133..136
FT /evidence="ECO:0007829|PDB:3UN7"
FT HELIX 140..152
FT /evidence="ECO:0007829|PDB:3UN7"
FT STRAND 160..165
FT /evidence="ECO:0007829|PDB:3UN7"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:3UN7"
FT STRAND 171..179
FT /evidence="ECO:0007829|PDB:3UN7"
FT HELIX 183..186
FT /evidence="ECO:0007829|PDB:3UN7"
FT HELIX 191..203
FT /evidence="ECO:0007829|PDB:3UN7"
FT TURN 212..214
FT /evidence="ECO:0007829|PDB:3UN7"
FT HELIX 221..224
FT /evidence="ECO:0007829|PDB:3UN7"
FT HELIX 225..234
FT /evidence="ECO:0007829|PDB:3UN7"
FT STRAND 241..244
FT /evidence="ECO:0007829|PDB:3UN7"
FT STRAND 247..250
FT /evidence="ECO:0007829|PDB:3UN7"
FT STRAND 257..259
FT /evidence="ECO:0007829|PDB:3UN7"
FT HELIX 261..263
FT /evidence="ECO:0007829|PDB:3UN7"
FT STRAND 266..273
FT /evidence="ECO:0007829|PDB:3UN7"
FT HELIX 274..280
FT /evidence="ECO:0007829|PDB:3UN7"
FT HELIX 283..293
FT /evidence="ECO:0007829|PDB:3UN7"
FT HELIX 295..304
FT /evidence="ECO:0007829|PDB:3UN7"
FT TURN 305..308
FT /evidence="ECO:0007829|PDB:3UN7"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:3UN7"
FT HELIX 329..335
FT /evidence="ECO:0007829|PDB:3UN7"
FT TURN 336..338
FT /evidence="ECO:0007829|PDB:3UN7"
FT HELIX 346..357
FT /evidence="ECO:0007829|PDB:3UN7"
FT TURN 358..360
FT /evidence="ECO:0007829|PDB:3UN7"
FT STRAND 361..363
FT /evidence="ECO:0007829|PDB:3UN7"
FT STRAND 366..372
FT /evidence="ECO:0007829|PDB:3UN7"
FT STRAND 378..381
FT /evidence="ECO:0007829|PDB:3UN7"
FT STRAND 386..389
FT /evidence="ECO:0007829|PDB:3UN7"
FT HELIX 393..408
FT /evidence="ECO:0007829|PDB:3UN7"
FT STRAND 422..428
FT /evidence="ECO:0007829|PDB:3UN7"
FT STRAND 431..433
FT /evidence="ECO:0007829|PDB:3UPO"
FT TURN 434..436
FT /evidence="ECO:0007829|PDB:3UN7"
FT STRAND 440..448
FT /evidence="ECO:0007829|PDB:3UN7"
FT STRAND 453..460
FT /evidence="ECO:0007829|PDB:3UN7"
FT HELIX 463..465
FT /evidence="ECO:0007829|PDB:3UPO"
FT STRAND 466..471
FT /evidence="ECO:0007829|PDB:3UN7"
FT HELIX 475..487
FT /evidence="ECO:0007829|PDB:3UN7"
SQ SEQUENCE 491 AA; 51576 MW; 888DBA26BE251581 CRC64;
MNASLRRISV TVMALIVLLL LNATMTQVFT ADGLRADPRN QRVLLDEYSR QRGQITAGGQ
LLAYSVATDG RFRFLRVYPN PEVYAPVTGF YSLRYSSTAL ERAEDPILNG SDRRLFGRRL
ADFFTGRDPR GGNVDTTINP RIQQAGWDAM QQGCYGPCKG AVVALEPSTG KILALVSSPS
YDPNLLASHN PEVQAQAWQR LGDNPASPLT NRAISETYPP GSTFKVITTA AALAAGATET
EQLTAAPTIP LPGSTAQLEN YGGAPCGDEP TVSLREAFVK SCNTAFVQLG IRTGADALRS
MARAFGLDSP PRPTPLQVAE STVGPIPDSA ALGMTSIGQK DVALTPLANA EIAATIANGG
ITMRPYLVGS LKGPDLANIS TTVGYQQRRA VSPQVAAKLT ELMVGAEKVA QQKGAIPGVQ
IASKTGTAEH GTDPRHTPPH AWYIAFAPAQ APKVAVAVLV ENGADRLSAT GGALAAPIGR
AVIEAALQGE P
