DACB2_MYCTU
ID DACB2_MYCTU Reviewed; 291 AA.
AC I6Y204;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=D-alanyl-D-alanine carboxypeptidase DacB2 {ECO:0000305};
DE Short=D,D-carboxypeptidase DacB2 {ECO:0000303|PubMed:22906310};
DE Short=DD-carboxypeptidase {ECO:0000305};
DE Short=DD-peptidase {ECO:0000305};
DE EC=3.4.16.- {ECO:0000269|PubMed:22906310};
DE Flags: Precursor;
GN Name=dacB2 {ECO:0000303|PubMed:22138550};
GN OrderedLocusNames=Rv2911 {ECO:0000312|EMBL:CCP45713.1};
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] {ECO:0007744|PubMed:21969609}
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [3]
RP DISRUPTION PHENOTYPE, AND OVEREXPRESSION.
RC STRAIN=H37Rv;
RX PubMed=22138550; DOI=10.1016/j.micpath.2011.11.003;
RA Bourai N., Jacobs W.R. Jr., Narayanan S.;
RT "Deletion and overexpression studies on DacB2, a putative low molecular
RT mass penicillin binding protein from Mycobacterium tuberculosis H(37)Rv.";
RL Microb. Pathog. 52:109-116(2012).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=22906310; DOI=10.1111/j.1365-2958.2012.08199.x;
RA Kumar P., Arora K., Lloyd J.R., Lee I.Y., Nair V., Fischer E.,
RA Boshoff H.I., Barry C.E. III;
RT "Meropenem inhibits D,D-carboxypeptidase activity in Mycobacterium
RT tuberculosis.";
RL Mol. Microbiol. 86:367-381(2012).
RN [5]
RP FUNCTION, PATHWAY, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=25467937; DOI=10.1016/j.micres.2014.10.002;
RA Kandasamy S., Narayanan S.;
RT "Phenotypic characterization of a novel double knockout PknI/DacB2 from
RT Mycobacterium tuberculosis.";
RL Microbiol. Res. 170:255-262(2015).
RN [6] {ECO:0007744|PDB:4P0M}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 25-291 OF MUTANT IN COMPLEX WITH
RP PMSF, FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND ACTIVE SITE.
RX PubMed=25551456; DOI=10.1371/journal.pone.0116249;
RA Prigozhin D.M., Krieger I.V., Huizar J.P., Mavrici D., Waldo G.S.,
RA Hung L.W., Sacchettini J.C., Terwilliger T.C., Alber T.;
RT "Subfamily-specific adaptations in the structures of two penicillin-binding
RT proteins from Mycobacterium tuberculosis.";
RL PLoS ONE 9:e116249-e116249(2014).
RN [7] {ECO:0007744|PDB:4RYE}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 26-291.
RC STRAIN=H37Rv;
RA Cuff M., Tan K., Hatzos-Skintges C., Jedrzejczak R., Sacchettini J.,
RA Joachimiak A.;
RT "The crystal structure of D-alanyl-D-alanine carboxypeptidase from
RT Mycobacterium tuberculosis H37Rv.";
RL Submitted (DEC-2014) to the PDB data bank.
CC -!- FUNCTION: Probably cleaves the terminal D-Ala-D-Ala dipeptide of the
CC peptidoglycan stem peptide (Probable). Shows significant D,D-
CC carboxypeptidase activity in vitro (PubMed:22906310). Acts on the
CC synthetic penta-peptide substrate Penta-DAP (L-Ala-gamma-D-Gln-DAP-D-
CC Ala-D-Ala). Shows also weak activity on Penta-Lys (L-Ala-gamma-Glu-L-
CC Lys-D-Ala-D-Ala) (PubMed:22906310). The catalytic domain binds weakly
CC to peptidoglycan in vitro (PubMed:25551456). Plays an important role in
CC the maintenance of colony morphology and cell wall permeability and
CC integrity (PubMed:25467937). {ECO:0000269|PubMed:22906310,
CC ECO:0000269|PubMed:25467937, ECO:0000269|PubMed:25551456,
CC ECO:0000305|PubMed:22906310}.
CC -!- ACTIVITY REGULATION: Inhibited by the beta-lactam antibiotic meropenem
CC (PubMed:22906310). Inhibited by the non-specific inhibitor
CC phenylmethylsulfonyl fluoride (PMSF) (Probable).
CC {ECO:0000269|PubMed:22906310, ECO:0000305|PubMed:25551456}.
CC -!- PATHWAY: Cell wall biogenesis; peptidoglycan biosynthesis.
CC {ECO:0000305|PubMed:25467937}.
CC -!- SUBCELLULAR LOCATION: Periplasm {ECO:0000305|PubMed:25551456}.
CC -!- DISRUPTION PHENOTYPE: Deletion of the gene results in reduced growth in
CC acidic medium under low oxygen conditions. The mutant shows better
CC intracellular growth and survival inside THP-1 cells compared to wild-
CC type and complemented strains. The colony morphology and antibiotic
CC sensitivity of mutant and wild-type strains are similar
CC (PubMed:22138550). The double knockout mutant pknI/dacB2 shows smoother
CC colony morphology on solid agar and exhibits defective biofilm and cord
CC formation. Double mutant is hypersensitive to cell wall damaging agents
CC such as lysozyme, malachite green, ethidium bromide and to isoniazid, a
CC first line anti-TB drug (PubMed:25467937).
CC {ECO:0000269|PubMed:22138550, ECO:0000269|PubMed:25467937}.
CC -!- MISCELLANEOUS: Overexpression in Mycobacterium smegmatis results in
CC reduced growth, an altered colony morphology, and a defect in sliding
CC motility and biofilm formation. Overexpression of the S69C mutant shows
CC similar results, indicating that the effects produced are independent
CC of protein's penicillin binding function.
CC {ECO:0000269|PubMed:22138550}.
CC -!- SIMILARITY: Belongs to the peptidase S11 family. {ECO:0000305}.
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DR EMBL; AL123456; CCP45713.1; -; Genomic_DNA.
DR RefSeq; WP_003414736.1; NZ_NVQJ01000006.1.
DR RefSeq; YP_177914.1; NC_000962.3.
DR PDB; 4P0M; X-ray; 2.00 A; A=25-291.
DR PDB; 4RYE; X-ray; 1.90 A; A/B/C/D=26-291.
DR PDBsum; 4P0M; -.
DR PDBsum; 4RYE; -.
DR AlphaFoldDB; I6Y204; -.
DR SMR; I6Y204; -.
DR STRING; 83332.Rv2911; -.
DR PaxDb; I6Y204; -.
DR PRIDE; I6Y204; -.
DR DNASU; 887189; -.
DR GeneID; 45426898; -.
DR GeneID; 887189; -.
DR KEGG; mtu:Rv2911; -.
DR PATRIC; fig|83332.111.peg.3240; -.
DR TubercuList; Rv2911; -.
DR eggNOG; COG1686; Bacteria.
DR OMA; WDIKLTK; -.
DR PhylomeDB; I6Y204; -.
DR UniPathway; UPA00219; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0042597; C:periplasmic space; IEA:UniProtKB-SubCell.
DR GO; GO:0009002; F:serine-type D-Ala-D-Ala carboxypeptidase activity; IEA:InterPro.
DR GO; GO:0071555; P:cell wall organization; IEA:UniProtKB-KW.
DR GO; GO:0009252; P:peptidoglycan biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
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; IPR018044; Peptidase_S11.
DR InterPro; IPR001967; Peptidase_S11_N.
DR Pfam; PF00768; Peptidase_S11; 1.
DR PRINTS; PR00725; DADACBPTASE1.
DR SUPFAM; SSF56601; SSF56601; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Carboxypeptidase; Cell shape;
KW Cell wall biogenesis/degradation; Hydrolase; Peptidoglycan synthesis;
KW Periplasm; Protease; Reference proteome; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..291
FT /note="D-alanyl-D-alanine carboxypeptidase DacB2"
FT /id="PRO_5010244966"
FT ACT_SITE 69
FT /note="Acyl-ester intermediate"
FT /evidence="ECO:0000305|PubMed:25551456"
FT ACT_SITE 72
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P0AEB2"
FT ACT_SITE 124
FT /evidence="ECO:0000250|UniProtKB:P0AEB2"
FT STRAND 43..49
FT /evidence="ECO:0007829|PDB:4RYE"
FT TURN 50..52
FT /evidence="ECO:0007829|PDB:4RYE"
FT STRAND 54..60
FT /evidence="ECO:0007829|PDB:4RYE"
FT HELIX 68..71
FT /evidence="ECO:0007829|PDB:4RYE"
FT HELIX 72..82
FT /evidence="ECO:0007829|PDB:4RYE"
FT STRAND 88..90
FT /evidence="ECO:0007829|PDB:4RYE"
FT HELIX 93..96
FT /evidence="ECO:0007829|PDB:4RYE"
FT STRAND 110..112
FT /evidence="ECO:0007829|PDB:4RYE"
FT HELIX 113..122
FT /evidence="ECO:0007829|PDB:4RYE"
FT HELIX 126..135
FT /evidence="ECO:0007829|PDB:4RYE"
FT HELIX 139..152
FT /evidence="ECO:0007829|PDB:4RYE"
FT STRAND 161..166
FT /evidence="ECO:0007829|PDB:4RYE"
FT HELIX 177..188
FT /evidence="ECO:0007829|PDB:4RYE"
FT HELIX 191..198
FT /evidence="ECO:0007829|PDB:4RYE"
FT STRAND 200..206
FT /evidence="ECO:0007829|PDB:4RYE"
FT STRAND 209..214
FT /evidence="ECO:0007829|PDB:4RYE"
FT HELIX 219..222
FT /evidence="ECO:0007829|PDB:4RYE"
FT STRAND 226..234
FT /evidence="ECO:0007829|PDB:4RYE"
FT TURN 235..237
FT /evidence="ECO:0007829|PDB:4RYE"
FT STRAND 238..247
FT /evidence="ECO:0007829|PDB:4RYE"
FT STRAND 250..259
FT /evidence="ECO:0007829|PDB:4RYE"
FT HELIX 268..281
FT /evidence="ECO:0007829|PDB:4RYE"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:4RYE"
SQ SEQUENCE 291 AA; 29747 MW; BE6282F8DDAFB3B8 CRC64;
MRKLMTATAA LCACAVTVSA GAAWADADVQ PAGSVPIPDG PAQTWIVADL DSGQVLAGRD
QNVAHPPAST IKVLLALVAL DELDLNSTVV ADVADTQAEC NCVGVKPGRS YTARQLLDGL
LLVSGNDAAN TLAHMLGGQD VTVAKMNAKA ATLGATSTHA TTPSGLDGPG GSGASTAHDL
VVIFRAAMAN PVFAQITAEP SAMFPSDNGE QLIVNQDELL QRYPGAIGGK TGYTNAARKT
FVGAAARGGR RLVIAMMYGL VKEGGPTYWD QAATLFDWGF ALNPQASVGS L
