RIPA_MYCTU
ID RIPA_MYCTU Reviewed; 472 AA.
AC O53168; L0T6Z1;
DT 16-NOV-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Peptidoglycan endopeptidase RipA;
DE EC=3.4.-.-;
DE AltName: Full=Macrophage invasion and intracellular persistence protein A;
DE AltName: Full=Resuscitation-promoting factor interaction partner A;
DE Short=Rpf-interacting protein A;
DE Flags: Precursor;
GN Name=ripA; OrderedLocusNames=Rv1477;
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 FUNCTION IN HOST CELL INVASION AND SURVIVAL IN HOST MACROPHAGES, AND
RP MUTAGENESIS OF 419-ARG--ASP-421 AND 382-ASP--GLU-385.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16495549; DOI=10.1128/iai.74.3.1757-1767.2006;
RA Gao L.Y., Pak M., Kish R., Kajihara K., Brown E.J.;
RT "A mycobacterial operon essential for virulence in vivo and invasion and
RT intracellular persistence in macrophages.";
RL Infect. Immun. 74:1757-1767(2006).
RN [3]
RP FUNCTION, INTERACTION WITH RPFB AND RPFE, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17919286; DOI=10.1111/j.1365-2958.2007.05945.x;
RA Hett E.C., Chao M.C., Steyn A.J., Fortune S.M., Deng L.L., Rubin E.J.;
RT "A partner for the resuscitation-promoting factors of Mycobacterium
RT tuberculosis.";
RL Mol. Microbiol. 66:658-668(2007).
RN [4]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [5]
RP FUNCTION IN CELL DIVISION, AND FUNCTION IN PEPTIDOGLYCAN DEGRADATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18463693; DOI=10.1371/journal.ppat.1000001;
RA Hett E.C., Chao M.C., Deng L.L., Rubin E.J.;
RT "A mycobacterial enzyme essential for cell division synergizes with
RT resuscitation-promoting factor.";
RL PLoS Pathog. 4:E1000001-E1000001(2008).
RN [6]
RP INTERACTION WITH PBP1A, AND ACTIVITY REGULATION.
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 [7]
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 [8]
RP X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 263-472, FUNCTION IN PEPTIDOGLYCAN
RP DEGRADATION, SUBUNIT, CATALYTIC ACTIVITY, MUTAGENESIS OF CYS-383, ACTIVE
RP SITE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20826344; DOI=10.1016/j.str.2010.06.007;
RA Ruggiero A., Marasco D., Squeglia F., Soldini S., Pedone E., Pedone C.,
RA Berisio R.;
RT "Structure and functional regulation of RipA, a mycobacterial enzyme
RT essential for daughter cell separation.";
RL Structure 18:1184-1190(2010).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 264-472.
RA Tizzano B., Pogenberg V., Wilmanns M.;
RT "Structure of Rv1477, hypothetical invasion protein of Mycobacterium
RT tuberculosis.";
RL Submitted (JUL-2010) to the PDB data bank.
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.38 ANGSTROMS) OF 260-472, FUNCTION, CATALYTIC
RP ACTIVITY, PEPTIDOGLYCAN BINDING, AND SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21864539; DOI=10.1016/j.jmb.2011.08.014;
RA Both D., Schneider G., Schnell R.;
RT "Peptidoglycan remodeling in Mycobacterium tuberculosis: comparison of
RT structures and catalytic activities of RipA and RipB.";
RL J. Mol. Biol. 413:247-260(2011).
CC -!- FUNCTION: Peptidoglycan endopeptidase that cleaves the bond between D-
CC glutamate and meso-diaminopimelate. Binds and degrades high-molecular
CC weight peptidoglycan from a number of Actinobacteria; activity is
CC increased in the presence of RpfB and inhibited by PBP1A (ponA1).
CC Required for normal separation of daughter cells after cell division
CC and for cell wall integrity. Required for host cell invasion and
CC intracellular survival in host macrophages.
CC {ECO:0000269|PubMed:16495549, ECO:0000269|PubMed:17919286,
CC ECO:0000269|PubMed:18463693, ECO:0000269|PubMed:20826344,
CC ECO:0000269|PubMed:21864539}.
CC -!- ACTIVITY REGULATION: The synergistic effects on peptidoglycan
CC degradation of RipA plus RpfB are inhibited by addition of PBP1A
CC (ponA1). {ECO:0000269|PubMed:20686708}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is between 5 and 5.5.;
CC -!- SUBUNIT: Monomer. Interacts with RpfB and PBP1A (ponA1) via residues
CC 448-472 of RipA, interacts with RpfE. {ECO:0000269|PubMed:17919286,
CC ECO:0000269|PubMed:20686708, ECO:0000269|PubMed:20826344,
CC ECO:0000269|PubMed:21864539}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17919286}.
CC Note=Localizes to the septa upon expression in M.bovis or M.smegmatis.
CC Remains associated with the cell.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the peptidase C40 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01284, ECO:0000305}.
CC -!- CAUTION: The role of the N-terminal domain is controversial. A recent
CC paper (PubMed:21864539) found it had no effect on enzyme activity,
CC while another (PubMed:20826344) reported that it had an inhibitory role
CC and had to be cleaved off for full enzyme activity.
CC {ECO:0000305|PubMed:20826344, ECO:0000305|PubMed:21864539}.
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DR EMBL; AL123456; CCP44237.1; -; Genomic_DNA.
DR PIR; H70873; H70873.
DR RefSeq; NP_215993.1; NC_000962.3.
DR RefSeq; WP_003407523.1; NZ_NVQJ01000004.1.
DR PDB; 2XIV; X-ray; 1.40 A; A=264-472.
DR PDB; 3NE0; X-ray; 1.00 A; A=263-472.
DR PDB; 3PBC; X-ray; 1.38 A; A=260-472.
DR PDB; 3S0Q; X-ray; 1.45 A; A=260-472.
DR PDB; 4Q4G; X-ray; 0.97 A; X=1-472.
DR PDB; 4Q4N; X-ray; 1.38 A; A=1-472.
DR PDB; 4Q4T; X-ray; 1.63 A; A=1-472.
DR PDB; 6EWY; X-ray; 2.20 A; A=39-255.
DR PDBsum; 2XIV; -.
DR PDBsum; 3NE0; -.
DR PDBsum; 3PBC; -.
DR PDBsum; 3S0Q; -.
DR PDBsum; 4Q4G; -.
DR PDBsum; 4Q4N; -.
DR PDBsum; 4Q4T; -.
DR PDBsum; 6EWY; -.
DR AlphaFoldDB; O53168; -.
DR SMR; O53168; -.
DR STRING; 83332.Rv1477; -.
DR PaxDb; O53168; -.
DR DNASU; 886541; -.
DR GeneID; 886541; -.
DR KEGG; mtu:Rv1477; -.
DR TubercuList; Rv1477; -.
DR eggNOG; COG0791; Bacteria.
DR eggNOG; COG3883; Bacteria.
DR InParanoid; O53168; -.
DR OMA; AYMNGPS; -.
DR EvolutionaryTrace; O53168; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; IDA:MTBBASE.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0008745; F:N-acetylmuramoyl-L-alanine amidase activity; IDA:MTBBASE.
DR GO; GO:0071555; P:cell wall organization; IEA:UniProtKB-KW.
DR GO; GO:0071554; P:cell wall organization or biogenesis; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR DisProt; DP02505; -.
DR InterPro; IPR000064; NLP_P60_dom.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR Pfam; PF00877; NLPC_P60; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS51935; NLPC_P60; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell wall biogenesis/degradation; Hydrolase; Protease;
KW Reference proteome; Secreted; Signal; Thiol protease.
FT SIGNAL 1..39
FT /evidence="ECO:0000305"
FT CHAIN 40..472
FT /note="Peptidoglycan endopeptidase RipA"
FT /id="PRO_0000413762"
FT DOMAIN 340..472
FT /note="NlpC/P60"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01284"
FT ACT_SITE 383
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01284"
FT ACT_SITE 432
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01284"
FT ACT_SITE 444
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01284,
FT ECO:0000305|PubMed:20826344"
FT MUTAGEN 382..385
FT /note="DCSG->AAAA: Abolishes host cell invasion and
FT survival in host macrophages."
FT /evidence="ECO:0000269|PubMed:16495549"
FT MUTAGEN 383
FT /note="C->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:20826344"
FT MUTAGEN 419..421
FT /note="RGD->AGA: Abolishes host cell invasion."
FT /evidence="ECO:0000269|PubMed:16495549"
FT HELIX 45..125
FT /evidence="ECO:0007829|PDB:6EWY"
FT TURN 128..131
FT /evidence="ECO:0007829|PDB:6EWY"
FT HELIX 138..237
FT /evidence="ECO:0007829|PDB:6EWY"
FT STRAND 284..288
FT /evidence="ECO:0007829|PDB:4Q4G"
FT TURN 289..292
FT /evidence="ECO:0007829|PDB:4Q4G"
FT STRAND 293..296
FT /evidence="ECO:0007829|PDB:4Q4G"
FT HELIX 297..311
FT /evidence="ECO:0007829|PDB:4Q4G"
FT HELIX 336..338
FT /evidence="ECO:0007829|PDB:4Q4G"
FT HELIX 339..351
FT /evidence="ECO:0007829|PDB:4Q4G"
FT TURN 352..355
FT /evidence="ECO:0007829|PDB:4Q4G"
FT HELIX 373..375
FT /evidence="ECO:0007829|PDB:4Q4G"
FT STRAND 379..381
FT /evidence="ECO:0007829|PDB:4Q4G"
FT HELIX 383..392
FT /evidence="ECO:0007829|PDB:4Q4G"
FT TURN 393..395
FT /evidence="ECO:0007829|PDB:4Q4G"
FT HELIX 402..406
FT /evidence="ECO:0007829|PDB:4Q4G"
FT STRAND 408..413
FT /evidence="ECO:0007829|PDB:4Q4G"
FT HELIX 414..416
FT /evidence="ECO:0007829|PDB:4Q4G"
FT STRAND 422..426
FT /evidence="ECO:0007829|PDB:4Q4G"
FT HELIX 427..429
FT /evidence="ECO:0007829|PDB:4Q4G"
FT STRAND 431..438
FT /evidence="ECO:0007829|PDB:4Q4G"
FT STRAND 441..444
FT /evidence="ECO:0007829|PDB:4Q4G"
FT STRAND 451..456
FT /evidence="ECO:0007829|PDB:4Q4G"
FT STRAND 464..470
FT /evidence="ECO:0007829|PDB:4Q4G"
SQ SEQUENCE 472 AA; 49808 MW; 3B7D83D29E3631DD CRC64;
MRRNRRGSPA RPAARFVRPA IPSALSVALL VCTPGLATAD PQTDTIAALI ADVAKANQRL
QDLSDEVQAE QESVNKAMVD VETARDNAAA AEDDLEVSQR AVKDANAAIA AAQHRFDTFA
AATYMNGPSV SYLSASSPDE IIATVTAAKT LSASSQAVMA NLQRARTERV NTESAARLAK
QKADKAAADA KASQDAAVAA LTETRRKFDE QREEVQRLAA ERDAAQARLQ AARLVAWSSE
GGQGAPPFRM WDPGSGPAGG RAWDGLWDPT LPMIPSANIP GDPIAVVNQV LGISATSAQV
TANMGRKFLE QLGILQPTDT GITNAPAGSA QGRIPRVYGR QASEYVIRRG MSQIGVPYSW
GGGNAAGPSK GIDSGAGTVG FDCSGLVLYS FAGVGIKLPH YSGSQYNLGR KIPSSQMRRG
DVIFYGPNGS QHVTIYLGNG QMLEAPDVGL KVRVAPVRTA GMTPYVVRYI EY
