GLGM_MYCTU
ID GLGM_MYCTU Reviewed; 387 AA.
AC P9WMZ1; L0T8Z4; O05313; Q7D8L6;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=Alpha-maltose-1-phosphate synthase {ECO:0000303|PubMed:27513637};
DE Short=M1P synthase {ECO:0000303|PubMed:27513637};
DE EC=2.4.1.342 {ECO:0000269|PubMed:27513637};
DE AltName: Full=ADP-alpha-D-glucose:alpha-D-glucose-1-phosphate 4-alpha-D-glucosyltransferase {ECO:0000305|PubMed:27513637};
DE AltName: Full=M1P-producing glucosyltransferase {ECO:0000303|PubMed:27513637};
GN Name=glgM {ECO:0000303|PubMed:27513637}; Synonyms=glgA;
GN OrderedLocusNames=Rv1212c;
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, DISRUPTION PHENOTYPE, AND PATHWAY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18808383; DOI=10.1111/j.1365-2958.2008.06445.x;
RA Sambou T., Dinadayala P., Stadthagen G., Barilone N., Bordat Y.,
RA Constant P., Levillain F., Neyrolles O., Gicquel B., Lemassu A., Daffe M.,
RA Jackson M.;
RT "Capsular glucan and intracellular glycogen of Mycobacterium tuberculosis:
RT biosynthesis and impact on the persistence in mice.";
RL Mol. Microbiol. 70:762-774(2008).
RN [3]
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, DISRUPTION
RP PHENOTYPE, ACTIVITY REGULATION, PATHWAY, AND SUBSTRATE SPECIFICITY.
RX PubMed=27513637; DOI=10.1371/journal.ppat.1005768;
RA Koliwer-Brandl H., Syson K., van de Weerd R., Chandra G., Appelmelk B.,
RA Alber M., Ioerger T.R., Jacobs W.R. Jr., Geurtsen J., Bornemann S.,
RA Kalscheuer R.;
RT "Metabolic network for the biosynthesis of intra- and extracellular alpha-
RT glucans required for virulence of Mycobacterium tuberculosis.";
RL PLoS Pathog. 12:E1005768-E1005768(2016).
CC -!- FUNCTION: Involved in the biosynthesis of the maltose-1-phosphate (M1P)
CC building block required for alpha-glucan production by the key enzyme
CC GlgE (PubMed:18808383, PubMed:27513637). Catalyzes the formation of an
CC alpha-1,4 linkage between glucose from ADP-glucose and glucose 1-
CC phosphate (G1P) to yield maltose-1-phosphate (M1P) (PubMed:27513637).
CC Also able to catalyze the elongation of the non-reducing ends of
CC glycogen, maltodextrin and maltoheptaose using ADP-glucose as sugar
CC donor, however the rate of the reaction appears to be too low to be
CC physiologically relevant (PubMed:27513637). GlgM is also able to use
CC UDP-glucose as sugar donor with G1P, however, it is less efficient than
CC with ADP-glucose (PubMed:27513637). UDP-glucose is not used as sugar
CC donor when glycogen is used as acceptor (PubMed:27513637).
CC {ECO:0000269|PubMed:18808383, ECO:0000269|PubMed:27513637}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ADP-alpha-D-glucose + alpha-D-glucose 1-phosphate = ADP +
CC alpha-maltose 1-phosphate + H(+); Xref=Rhea:RHEA:50692,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57498, ChEBI:CHEBI:58601,
CC ChEBI:CHEBI:63576, ChEBI:CHEBI:456216; EC=2.4.1.342;
CC Evidence={ECO:0000269|PubMed:27513637};
CC -!- ACTIVITY REGULATION: Inhibited at high G1P concentrations.
CC {ECO:0000269|PubMed:27513637}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.046 mM for ADP-glucose (with 4 mM of G1P)
CC {ECO:0000269|PubMed:27513637};
CC KM=0.063 mM for ADP-glucose (with 2.5 mM of G1P)
CC {ECO:0000269|PubMed:27513637};
CC KM=0.121 mM for ADP-glucose (with 1 mM of G1P)
CC {ECO:0000269|PubMed:27513637};
CC KM=0.145 mM for ADP-glucose (with 0.25 mM of G1P)
CC {ECO:0000269|PubMed:27513637};
CC KM=0.4 mM for alpha-glucan {ECO:0000269|PubMed:27513637};
CC KM=0.695 mM for G1P (with 4 mM of ADP-glucose)
CC {ECO:0000269|PubMed:27513637};
CC KM=0.816 mM for G1P (with 0.1 mM of ADP-glucose)
CC {ECO:0000269|PubMed:27513637};
CC KM=0.9 mM for rabbit liver glycogen {ECO:0000269|PubMed:27513637};
CC KM=1.290 mM for G1P (with 0.5 mM of ADP-glucose)
CC {ECO:0000269|PubMed:27513637};
CC Vmax=136 umol/min/mg enzyme toward G1P (with 0.5 mM of ADP-glucose)
CC {ECO:0000269|PubMed:27513637};
CC Vmax=113 umol/min/mg enzyme toward G1P (with 4 mM of ADP-glucose)
CC {ECO:0000269|PubMed:27513637};
CC Vmax=54.2 umol/min/mg enzyme toward G1P (with 0.1 mM of ADP-glucose)
CC {ECO:0000269|PubMed:27513637};
CC Vmax=40.5 umol/min/mg enzyme toward ADP-glucose (with 1 mM of G1P)
CC {ECO:0000269|PubMed:27513637};
CC Vmax=27.7 umol/min/mg enzyme toward ADP-glucose (with 0.25 mM of G1P)
CC {ECO:0000269|PubMed:27513637};
CC Vmax=27.5 umol/min/mg enzyme toward ADP-glucose (with 2.5 mM of G1P)
CC {ECO:0000269|PubMed:27513637};
CC Vmax=21.4 umol/min/mg enzyme toward ADP-glucose (with 4 mM of G1P)
CC {ECO:0000269|PubMed:27513637};
CC Vmax=0.12 umol/min/mg enzyme with rabbit liver glycogen as substrate
CC {ECO:0000269|PubMed:27513637};
CC Vmax=0.02 umol/min/mg enzyme with alpha-glucan as substrate
CC {ECO:0000269|PubMed:27513637};
CC Note=kcat is 97.9 sec(-1) for G1P as substrate (with 0.5 mM of ADP-
CC glucose). kcat is 80.6 sec(-1) for G1P as substrate (with 4 mM of
CC ADP-glucose). kcat is 39 sec(-1) for G1P as substrate (with 0.1 mM of
CC ADP-glucose). kcat is 29.2 sec(-1) for ADP-glucose as substrate (with
CC 1 mM of G1P). kcat is 20 sec(-1) for ADP-glucose as substrate (with
CC 0.25 mM of G1P). kcat is 19.8 sec(-1) for ADP-glucose as substrate
CC (with 2.5 mM of G1P). kcat is 15.4 sec(-1) for ADP-glucose as
CC substrate (with 4 mM of G1P). kcat is 0.09 sec(-1) for rabbit liver
CC glycogen as substrate. kcat is 0.014 sec(-1) for alpha-glucan as
CC substrate. {ECO:0000269|PubMed:27513637};
CC -!- PATHWAY: Capsule biogenesis; capsule polysaccharide biosynthesis.
CC {ECO:0000269|PubMed:18808383, ECO:0000269|PubMed:27513637}.
CC -!- PATHWAY: Glycan biosynthesis; glycogen biosynthesis.
CC {ECO:0000269|PubMed:18808383, ECO:0000269|PubMed:27513637}.
CC -!- DISRUPTION PHENOTYPE: Inactivation of glgM affects the production of
CC extracellular alpha-glucan (two-fold reduction), but not that of
CC intracellular glycogen and 6-O-methylglucosyl lipopolysaccharides
CC (MGLP) (PubMed:18808383, PubMed:27513637). Cells lacking this gene are
CC also impaired in their ability to persist in both the spleen and the
CC lungs of mice (PubMed:18808383). Combined inactivation of both glgM and
CC ostA is lethal, potentially due to accumulation of toxic levels of ADP-
CC glucose (PubMed:27513637). Combined inactivation of both glgM and treS
CC results in absence of alpha-glucan (PubMed:27513637).
CC {ECO:0000269|PubMed:18808383, ECO:0000269|PubMed:27513637}.
CC -!- MISCELLANEOUS: Maltose-1-phosphate (M1P) is generated by two
CC alternative routes: the TreS-Pep2 branch and the GlgC-GlgM branch,
CC however it seems that TreS-Pep2 branch provides most of M1P for the
CC GlgE pathway in M.tuberculosis. {ECO:0000269|PubMed:27513637}.
CC -!- MISCELLANEOUS: Attempts to disrupt both the Rv3032 gene and glgA in
CC order to create a mutant simultaneously deficient in both alpha-1,4-
CC glucosyltransferases turned out to be unsuccessful. Thus,
CC M.tuberculosis H37Rv requires a functional copy of at least one of
CC these two genes for growth. {ECO:0000269|PubMed:18808383}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase group 1 family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP43968.1; -; Genomic_DNA.
DR PIR; B70610; B70610.
DR RefSeq; NP_215728.1; NC_000962.3.
DR RefSeq; WP_003898773.1; NZ_NVQJ01000039.1.
DR AlphaFoldDB; P9WMZ1; -.
DR SMR; P9WMZ1; -.
DR STRING; 83332.Rv1212c; -.
DR PaxDb; P9WMZ1; -.
DR GeneID; 887805; -.
DR KEGG; mtu:Rv1212c; -.
DR TubercuList; Rv1212c; -.
DR eggNOG; COG0297; Bacteria.
DR OMA; TREYPPD; -.
DR PhylomeDB; P9WMZ1; -.
DR BioCyc; MetaCyc:G185E-5382-MON; -.
DR BRENDA; 2.4.1.342; 3445.
DR UniPathway; UPA00164; -.
DR UniPathway; UPA00934; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0016757; F:glycosyltransferase activity; IBA:GO_Central.
DR GO; GO:0045227; P:capsule polysaccharide biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009250; P:glucan biosynthetic process; IMP:MTBBASE.
DR GO; GO:0005978; P:glycogen biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR001296; Glyco_trans_1.
DR InterPro; IPR028098; Glyco_trans_4-like_N.
DR InterPro; IPR011875; M1P_synthase.
DR Pfam; PF13439; Glyco_transf_4; 1.
DR Pfam; PF00534; Glycos_transf_1; 1.
DR TIGRFAMs; TIGR02149; glgA_Coryne; 1.
PE 1: Evidence at protein level;
KW Capsule biogenesis/degradation; Carbohydrate metabolism;
KW Glycosyltransferase; Reference proteome; Transferase.
FT CHAIN 1..387
FT /note="Alpha-maltose-1-phosphate synthase"
FT /id="PRO_0000413978"
SQ SEQUENCE 387 AA; 41533 MW; BC4C4B66980BAAFF CRC64;
MRVAMLTREY PPEVYGGAGV HVTELVAYLR RLCAVDVHCM GAPRPGAFAY RPDPRLGSAN
AALSTLSADL VMANAASAAT VVHSHTWYTA LAGHLAAILY DIPHVLTAHS LEPLRPWKKE
QLGGGYQVST WVEQTAVLAA NAVIAVSSAM RNDMLRVYPS LDPNLVHVIR NGIDTETWYP
AGPARTGSVL AELGVDPNRP MAVFVGRITR QKGVVHLVTA AHRFRSDVQL VLCAGAADTP
EVADEVRVAV AELARNRTGV FWIQDRLTIG QLREILSAAT VFVCPSVYEP LGIVNLEAMA
CATAVVASDV GGIPEVVADG ITGSLVHYDA DDATGYQARL AEAVNALVAD PATAERYGHA
GRQRCIQEFS WAYIAEQTLD IYRKVCA
