GLGE_MYCTU
ID GLGE_MYCTU Reviewed; 701 AA.
AC P9WQ17; L0T7Y4; P63531; Q10638;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 47.
DE RecName: Full=Alpha-1,4-glucan:maltose-1-phosphate maltosyltransferase;
DE Short=GMPMT;
DE EC=2.4.99.16;
DE AltName: Full=(1->4)-alpha-D-glucan:maltose-1-phosphate alpha-D-maltosyltransferase;
DE AltName: Full=(1->4)-alpha-D-glucan:phosphate alpha-D-maltosyltransferase;
GN Name=glgE; OrderedLocusNames=Rv1327c; ORFNames=MTCY130.12c;
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 DRUG TARGET.
RX PubMed=21180647; DOI=10.1358/dnp.2010.23.10.1534855;
RA Kalscheuer R., Jacobs W.R. Jr.;
RT "The significance of GlgE as a new target for tuberculosis.";
RL Drug News Perspect. 23:619-624(2010).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, ESSENTIALITY, DISRUPTION PHENOTYPE, AND DRUG TARGET.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20305657; DOI=10.1038/nchembio.340;
RA Kalscheuer R., Syson K., Veeraraghavan U., Weinrick B., Biermann K.E.,
RA Liu Z., Sacchettini J.C., Besra G., Bornemann S., Jacobs W.R. Jr.;
RT "Self-poisoning of Mycobacterium tuberculosis by targeting GlgE in an
RT alpha-glucan pathway.";
RL Nat. Chem. Biol. 6:376-384(2010).
RN [4]
RP SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21914799; DOI=10.1074/jbc.m111.279315;
RA Syson K., Stevenson C.E., Rejzek M., Fairhurst S.A., Nair A., Bruton C.J.,
RA Field R.A., Chater K.F., Lawson D.M., Bornemann S.;
RT "Structure of a Streptomyces maltosyltransferase GlgE: a homologue of a
RT genetically validated anti-tuberculosis target.";
RL J. Biol. Chem. 286:38298-38310(2011).
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: Essential maltosyltransferase that uses maltose 1-phosphate
CC (M1P) as the sugar donor to elongate linear or branched alpha-(1->4)-
CC glucans. Maltooligosaccharides with a degree of polymerization (DP)
CC superior or equal to 4 are efficient acceptors, with DP5 being optimal
CC in the GlgE-catalyzed polymerization with M1P. Is specific for the
CC alpha-anomer of M1P as substrate, since the beta-anomer of M1P gives no
CC activity. Exhibits an alpha-retaining catalytic mechanism. Is also able
CC to catalyze the reverse reaction in vitro, releasing M1P from glycogen
CC in the presence of inorganic phosphate. Also catalyzes
CC disproportionation reactions through maltosyl transfer between
CC maltooligosaccharides. Is involved in a branched alpha-glucan
CC biosynthetic pathway from trehalose, together with TreS, Mak and GlgB.
CC {ECO:0000269|PubMed:20305657}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[(1->4)-alpha-D-glucosyl](n) + alpha-maltose 1-phosphate =
CC [(1->4)-alpha-D-glucosyl](n+2) + phosphate; Xref=Rhea:RHEA:42692,
CC Rhea:RHEA-COMP:9584, Rhea:RHEA-COMP:10183, ChEBI:CHEBI:15444,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:63576; EC=2.4.99.16;
CC Evidence={ECO:0000269|PubMed:20305657};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=35 mM for maltohexaose (in the presence of 5 mM M1P)
CC {ECO:0000269|PubMed:20305657};
CC KM=13.3 mM for maltohexaose (in the presence of 1 mM M1P)
CC {ECO:0000269|PubMed:20305657};
CC KM=0.25 mM for alpha-maltose 1-phosphate
CC {ECO:0000269|PubMed:20305657};
CC KM=6 mM for phosphate {ECO:0000269|PubMed:20305657};
CC pH dependence:
CC Optimum pH is 7.0 with maltohexaose as acceptor substrate.
CC {ECO:0000269|PubMed:20305657};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius with maltohexaose as
CC acceptor substrate. {ECO:0000269|PubMed:20305657};
CC -!- PATHWAY: Glycan biosynthesis; glycogen biosynthesis.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:21914799}.
CC -!- DISRUPTION PHENOTYPE: GlgE inactivation causes rapid death of
CC M.tuberculosis in vitro and in mice through a self-poisoning
CC accumulation of maltose 1-phosphate, driven by a self-amplifying
CC feedback stress response. {ECO:0000269|PubMed:20305657}.
CC -!- MISCELLANEOUS: The unique combination of maltose 1-phosphate toxicity
CC and gene essentiality within a synthetic lethal pathway validates GlgE
CC as a distinct potential drug target that exploits new synergistic
CC mechanisms to induce death in M.tuberculosis.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 13 family. GlgE
CC subfamily. {ECO:0000305}.
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DR EMBL; AL123456; CCP44085.1; -; Genomic_DNA.
DR PIR; C70770; C70770.
DR RefSeq; NP_215843.2; NC_000962.3.
DR RefSeq; WP_003406897.1; NC_000962.3.
DR AlphaFoldDB; P9WQ17; -.
DR SMR; P9WQ17; -.
DR STRING; 83332.Rv1327c; -.
DR BindingDB; P9WQ17; -.
DR ChEMBL; CHEMBL3112377; -.
DR PaxDb; P9WQ17; -.
DR DNASU; 886895; -.
DR GeneID; 886895; -.
DR KEGG; mtu:Rv1327c; -.
DR PATRIC; fig|83332.111.peg.1482; -.
DR TubercuList; Rv1327c; -.
DR eggNOG; COG0366; Bacteria.
DR OMA; RPNFWPN; -.
DR PhylomeDB; P9WQ17; -.
DR BioCyc; MetaCyc:G185E-5506-MON; -.
DR BRENDA; 2.4.99.16; 3445.
DR UniPathway; UPA00164; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0016758; F:hexosyltransferase activity; IDA:MTBBASE.
DR GO; GO:0004553; F:hydrolase activity, hydrolyzing O-glycosyl compounds; IEA:InterPro.
DR GO; GO:0030979; P:alpha-glucan biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0005978; P:glycogen biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0005993; P:trehalose catabolic process; IMP:UniProtKB.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 2.60.40.1180; -; 1.
DR HAMAP; MF_02124; GlgE; 1.
DR InterPro; IPR026585; GlgE.
DR InterPro; IPR021828; GlgE_dom_N/S.
DR InterPro; IPR006047; Glyco_hydro_13_cat_dom.
DR InterPro; IPR013780; Glyco_hydro_b.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR InterPro; IPR013783; Ig-like_fold.
DR Pfam; PF00128; Alpha-amylase; 1.
DR Pfam; PF11896; DUF3416; 1.
DR SMART; SM00642; Aamy; 1.
DR SUPFAM; SSF51445; SSF51445; 1.
PE 1: Evidence at protein level;
KW Carbohydrate metabolism; Glycogen biosynthesis; Glycogen metabolism;
KW Glycosyltransferase; Reference proteome; Transferase.
FT CHAIN 1..701
FT /note="Alpha-1,4-glucan:maltose-1-phosphate
FT maltosyltransferase"
FT /id="PRO_0000054347"
FT REGION 286..317
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 418
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 447
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 288
FT /ligand="alpha-maltose 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:63576"
FT /evidence="ECO:0000250"
FT BINDING 348
FT /ligand="alpha-maltose 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:63576"
FT /evidence="ECO:0000250"
FT BINDING 383
FT /ligand="alpha-maltose 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:63576"
FT /evidence="ECO:0000250"
FT BINDING 419
FT /ligand="alpha-maltose 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:63576"
FT /evidence="ECO:0000250"
FT BINDING 557..558
FT /ligand="alpha-maltose 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:63576"
FT /evidence="ECO:0000250"
FT SITE 503
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
SQ SEQUENCE 701 AA; 78640 MW; EE637BA1DA7D694F CRC64;
MSGRAIGTET EWWVPGRVEI DDVAPVVSCG VYPAKAVVGE VVPVSAAVWR EGHEAVAATL
VVRYLGVRYP HLTDRPRARV LPTPSEPQQR VKPLLIPMTS GQEPFVFHGQ FTPDRVGLWT
FRVDGWGDPI HTWRHGLIAK LDAGQGETEL SNDLLVGAVL LERAATGVPR GLRDPLLAAA
AALRTPGDPV TRTALALTPE IEELLADYPL RDLVTRGEQF GVWVDRPLAR FGAWYEMFPR
STGGWDDDGN PVHGTFATAA AELPRIAGMG FDVVYLPPIH PIGKVHRKGR NNSPTAAPTD
VGSPWAIGSD EGGHDTVHPS LGTIDDFDDF VSAARDLGME VALDLALQCA PDHPWAREHR
QWFTELPDGT IAYAENPPKK YQDIYPLNFD NDPEGLYDEV LRVVQHWVNH GVKFFRVDNP
HTKPPNFWAW LIAQVKTVDP DVLFLSEAFT PPARQYGLAK LGFTQSYSYF TWRTTKWELT
EFGNQIAELA DYRRPNLFVN TPDILHAVLQ HNGPGMFAIR AVLAATMSPA WGMYCGYELF
EHRAVREGSE EYLDSEKYEL RPRDFASALD QGRSLQPFIT RLNIIRRLHP AFQQLRTIHF
HHVDNDALLA YSKFDPATGD CVLVVVTLNA FGPEEATLWL DMAALGMEDY DRFWVRDEIT
GEEYQWGQAN YIRIDPARAV AHIINMPAVP YESRNTLLRR R
