PBP1A_MYCTU
ID PBP1A_MYCTU Reviewed; 820 AA.
AC P71707; L0T5D2;
DT 06-FEB-2013, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2013, sequence version 3.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Penicillin-binding protein 1A;
DE Short=PBP-1A;
DE AltName: Full=Penicillin-binding protein 1*;
DE Includes:
DE RecName: Full=Penicillin-insensitive transglycosylase;
DE EC=2.4.1.129 {ECO:0000250|UniProtKB:P02918};
DE AltName: Full=Peptidoglycan TGase;
DE Includes:
DE RecName: Full=Penicillin-sensitive transpeptidase;
DE EC=3.4.16.4 {ECO:0000250|UniProtKB:P02918};
DE AltName: Full=DD-transpeptidase;
GN Name=ponA1; OrderedLocusNames=Rv0050; ORFNames=MTCY21D4.13;
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 PROTEIN SEQUENCE OF 97-114, AND SEQUENCE REVISION TO N-TERMINUS.
RC STRAIN=H37Rv;
RX PubMed=34915127; DOI=10.1016/j.ygeno.2021.12.001;
RA Shi J., Meng S., Wan L., Zhang Z., Jiang S., Zhu H., Dai E., Chang L.,
RA Gao H., Wan K., Zhang L., Zhao X., Liu H., Lyu Z., Zhang Y., Xu P.;
RT "Deep N-terminomics of Mycobacterium tuberculosis H37Rv extensively correct
RT annotated encoding genes.";
RL Genomics 114:292-304(2021).
RN [3]
RP PENICILLIN-BINDING.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11802794; DOI=10.1042/0264-6021:3610635;
RA Bhakta S., Basu J.;
RT "Overexpression, purification and biochemical characterization of a class A
RT high-molecular-mass penicillin-binding protein (PBP), PBP1* and its soluble
RT derivative from Mycobacterium tuberculosis.";
RL Biochem. J. 361:635-639(2002).
RN [4]
RP FUNCTION, INTERACTION WITH RIPA, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20686708; DOI=10.1371/journal.ppat.1001020;
RA Hett E.C., Chao M.C., Rubin E.J.;
RT "Interaction and modulation of two antagonistic cell wall enzymes of
RT mycobacteria.";
RL PLoS Pathog. 6:E1001020-E1001020(2010).
RN [5]
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).
CC -!- FUNCTION: Cell wall formation. Synthesis of cross-linked peptidoglycan
CC from the lipid intermediates. The enzyme has a penicillin-insensitive
CC transglycosylase N-terminal domain (formation of linear glycan strands)
CC and a penicillin-sensitive transpeptidase C-terminal domain (cross-
CC linking of the peptide subunits) (By similarity). Has little
CC peptidoglycan hydrolytic activity; however it inhibits the synergistic
CC peptidoglycan hydrolysis of RipA plus RpfB. {ECO:0000250,
CC ECO:0000269|PubMed:20686708}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-
CC Ala)](n)-di-trans,octa-cis-undecaprenyl diphosphate + beta-D-GlcNAc-
CC (1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-di-trans,octa-
CC cis-undecaprenyl diphosphate = [GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-
CC D-Glu-L-Lys-D-Ala-D-Ala)](n+1)-di-trans-octa-cis-undecaprenyl
CC diphosphate + di-trans,octa-cis-undecaprenyl diphosphate + H(+);
CC Xref=Rhea:RHEA:23708, Rhea:RHEA-COMP:9602, Rhea:RHEA-COMP:9603,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58405, ChEBI:CHEBI:60033,
CC ChEBI:CHEBI:78435; EC=2.4.1.129;
CC Evidence={ECO:0000250|UniProtKB:P02918};
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:0000250|UniProtKB:P02918};
CC -!- PATHWAY: Cell wall biogenesis; peptidoglycan biosynthesis.
CC -!- SUBUNIT: Interacts with RipA via its transpeptidase domain (residues
CC 561-820). {ECO:0000269|PubMed:20686708}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}. Note=Localizes to poles and occasionally septa
CC upon expression in M.smegmatis. {ECO:0000269|PubMed:20686708}.
CC -!- DOMAIN: A penicillin-binding domain is found between residues 420-820.
CC -!- SIMILARITY: In the N-terminal section; belongs to the
CC glycosyltransferase 51 family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the transpeptidase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CCP42772.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000269|PubMed:34915127};
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DR EMBL; AL123456; CCP42772.1; ALT_INIT; Genomic_DNA.
DR PIR; B70913; B70913.
DR RefSeq; YP_177687.1; NC_000962.3.
DR PDB; 5CRF; X-ray; 1.80 A; A/B/C/D=391-820.
DR PDB; 5CXW; X-ray; 1.75 A; A=391-820.
DR PDBsum; 5CRF; -.
DR PDBsum; 5CXW; -.
DR AlphaFoldDB; P71707; -.
DR SMR; P71707; -.
DR STRING; 83332.Rv0050; -.
DR CAZy; GT51; Glycosyltransferase Family 51.
DR PaxDb; P71707; -.
DR DNASU; 887065; -.
DR GeneID; 887065; -.
DR KEGG; mtu:Rv0050; -.
DR PATRIC; fig|83332.12.peg.56; -.
DR TubercuList; Rv0050; -.
DR eggNOG; COG0744; Bacteria.
DR InParanoid; P71707; -.
DR UniPathway; UPA00219; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030288; C:outer membrane-bounded periplasmic space; IDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008658; F:penicillin binding; IDA:MTBBASE.
DR GO; GO:0008955; F:peptidoglycan glycosyltransferase 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; IEA:UniProtKB-KW.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:MTBBASE.
DR GO; GO:0009252; P:peptidoglycan biosynthetic process; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
DR GO; GO:0046677; P:response to antibiotic; IBA:GO_Central.
DR Gene3D; 1.10.3810.10; -; 1.
DR Gene3D; 3.40.710.10; -; 1.
DR InterPro; IPR012338; Beta-lactam/transpept-like.
DR InterPro; IPR001264; Glyco_trans_51.
DR InterPro; IPR023346; Lysozyme-like_dom_sf.
DR InterPro; IPR036950; PBP_transglycosylase.
DR InterPro; IPR001460; PCN-bd_Tpept.
DR Pfam; PF00912; Transgly; 1.
DR Pfam; PF00905; Transpeptidase; 1.
DR SUPFAM; SSF53955; SSF53955; 1.
DR SUPFAM; SSF56601; SSF56601; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Carboxypeptidase; Cell membrane; Cell shape;
KW Cell wall biogenesis/degradation; Direct protein sequencing;
KW Glycosyltransferase; Hydrolase; Membrane; Multifunctional enzyme;
KW Peptidoglycan synthesis; Protease; Reference proteome; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..820
FT /note="Penicillin-binding protein 1A"
FT /id="PRO_0000421124"
FT TRANSMEM 139..159
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..120
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 180..360
FT /note="Transglycosylase"
FT REGION 453..743
FT /note="Transpeptidase"
FT REGION 792..820
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..17
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 97..111
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 800..820
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 213
FT /note="Proton donor; for transglycosylase activity"
FT /evidence="ECO:0000250|UniProtKB:P02919"
FT ACT_SITE 487
FT /note="Acyl-ester intermediate; for transpeptidase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:P02919"
FT HELIX 392..409
FT /evidence="ECO:0007829|PDB:5CXW"
FT HELIX 413..419
FT /evidence="ECO:0007829|PDB:5CXW"
FT STRAND 422..425
FT /evidence="ECO:0007829|PDB:5CXW"
FT HELIX 429..443
FT /evidence="ECO:0007829|PDB:5CXW"
FT STRAND 450..457
FT /evidence="ECO:0007829|PDB:5CXW"
FT TURN 459..461
FT /evidence="ECO:0007829|PDB:5CXW"
FT STRAND 463..468
FT /evidence="ECO:0007829|PDB:5CXW"
FT HELIX 486..489
FT /evidence="ECO:0007829|PDB:5CXW"
FT HELIX 490..499
FT /evidence="ECO:0007829|PDB:5CXW"
FT STRAND 507..509
FT /evidence="ECO:0007829|PDB:5CXW"
FT STRAND 513..515
FT /evidence="ECO:0007829|PDB:5CXW"
FT STRAND 518..520
FT /evidence="ECO:0007829|PDB:5CXW"
FT HELIX 523..525
FT /evidence="ECO:0007829|PDB:5CXW"
FT STRAND 529..532
FT /evidence="ECO:0007829|PDB:5CXW"
FT HELIX 533..539
FT /evidence="ECO:0007829|PDB:5CXW"
FT HELIX 542..551
FT /evidence="ECO:0007829|PDB:5CXW"
FT HELIX 555..566
FT /evidence="ECO:0007829|PDB:5CXW"
FT STRAND 575..577
FT /evidence="ECO:0007829|PDB:5CXW"
FT STRAND 583..585
FT /evidence="ECO:0007829|PDB:5CXW"
FT HELIX 590..594
FT /evidence="ECO:0007829|PDB:5CXW"
FT STRAND 597..599
FT /evidence="ECO:0007829|PDB:5CXW"
FT HELIX 601..612
FT /evidence="ECO:0007829|PDB:5CXW"
FT TURN 613..615
FT /evidence="ECO:0007829|PDB:5CXW"
FT STRAND 621..627
FT /evidence="ECO:0007829|PDB:5CXW"
FT STRAND 633..636
FT /evidence="ECO:0007829|PDB:5CXW"
FT TURN 637..639
FT /evidence="ECO:0007829|PDB:5CRF"
FT HELIX 650..660
FT /evidence="ECO:0007829|PDB:5CXW"
FT HELIX 663..666
FT /evidence="ECO:0007829|PDB:5CXW"
FT HELIX 673..675
FT /evidence="ECO:0007829|PDB:5CXW"
FT STRAND 679..686
FT /evidence="ECO:0007829|PDB:5CXW"
FT STRAND 690..702
FT /evidence="ECO:0007829|PDB:5CXW"
FT STRAND 705..716
FT /evidence="ECO:0007829|PDB:5CXW"
FT TURN 730..732
FT /evidence="ECO:0007829|PDB:5CXW"
FT HELIX 733..746
FT /evidence="ECO:0007829|PDB:5CXW"
FT STRAND 763..766
FT /evidence="ECO:0007829|PDB:5CXW"
SQ SEQUENCE 820 AA; 85969 MW; 6DD7A149081D3EB4 CRC64;
MNSDGRHHQS SSGAPRGPAN PGQRGQVPPD DRLTAILPPV TDDRSAPHAD SIEAVKAALD
GAPPMPPPRD PLEEVTAALA APPGKPPRGD QLGGRRRPPG PPGPPGSSGQ PAGRLPQPRV
DLPRVGQINW KWIRRSLYLT AAVVILLPMV TFTMAYLIVD VPKPGDIRTN QVSTILASDG
SEIAKIVPPE GNRVDVNLSQ VPMHVRQAVI AAEDRNFYSN PGFSFTGFAR AVKNNLFGGD
LQGGSTITQQ YVKNALVGSA QHGWSGLMRK AKELVIATKM SGEWSKDDVL QAYLNIIYFG
RGAYGISAAS KAYFDKPVEQ LTVAEGALLA ALIRRPSTLD PAVDPEGAHA RWNWVLDGMV
ETKALSPNDR AAQVFPETVP PDLARAENQT KGPNGLIERQ VTRELLELFN IDEQTLNTQG
LVVTTTIDPQ AQRAAEKAVA KYLDGQDPDM RAAVVSIDPH NGAVRAYYGG DNANGFDFAQ
AGLQTGSSFK VFALVAALEQ GIGLGYQVDS SPLTVDGIKI TNVEGEGCGT CNIAEALKMS
LNTSYYRLML KLNGGPQAVA DAAHQAGIAS SFPGVAHTLS EDGKGGPPNN GIVLGQYQTR
VIDMASAYAT LAASGIYHPP HFVQKVVSAN GQVLFDASTA DNTGDQRIPK AVADNVTAAM
EPIAGYSRGH NLAGGRDSAA KTGTTQFGDT TANKDAWMVG YTPSLSTAVW VGTVKGDEPL
VTASGAAIYG SGLPSDIWKA TMDGALKGTS NETFPKPTEV GGYAGVPPPP PPPEVPPSET
VIQPTVEIAP GITIPIGPPT TITLAPPPPA PPAATPTPPP
