KAD_MYCTU
ID KAD_MYCTU Reviewed; 181 AA.
AC P9WKF5; L0T7C0; O53796; P69440; P94927;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 41.
DE RecName: Full=Adenylate kinase {ECO:0000255|HAMAP-Rule:MF_00235};
DE Short=AK {ECO:0000255|HAMAP-Rule:MF_00235};
DE EC=2.7.4.3 {ECO:0000255|HAMAP-Rule:MF_00235};
DE AltName: Full=ATP-AMP transphosphorylase {ECO:0000255|HAMAP-Rule:MF_00235};
DE AltName: Full=ATP:AMP phosphotransferase {ECO:0000255|HAMAP-Rule:MF_00235};
DE AltName: Full=Adenylate monophosphate kinase {ECO:0000255|HAMAP-Rule:MF_00235};
GN Name=adk {ECO:0000255|HAMAP-Rule:MF_00235}; OrderedLocusNames=Rv0733;
GN ORFNames=MTV041.07;
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 N-TERMINUS, PARTIAL PROTEIN SEQUENCE, FUNCTION, MASS
RP SPECTROMETRY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND
RP CATALYTIC ACTIVITY.
RX PubMed=10398370;
RX DOI=10.1002/(sici)1097-0134(19990801)36:2<238::aid-prot9>3.0.co;2-k;
RA Munier-Lehmann H., Burlacu-Miron S., Craescu C.T., Mantsch H.H.,
RA Schultz C.P.;
RT "A new subfamily of short bacterial adenylate kinases with the
RT Mycobacterium tuberculosis enzyme as a model: a predictive and experimental
RT study.";
RL Proteins 36:238-248(1999).
RN [3]
RP PUPYLATION AT LYS-94, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20066036; DOI=10.1371/journal.pone.0008589;
RA Festa R.A., McAllister F., Pearce M.J., Mintseris J., Burns K.E.,
RA Gygi S.P., Darwin K.H.;
RT "Prokaryotic ubiquitin-like protein (Pup) proteome of Mycobacterium
RT tuberculosis.";
RL PLoS ONE 5:E8589-E8589(2010).
RN [4]
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 [5]
RP STRUCTURE BY NMR.
RX PubMed=14705932; DOI=10.1021/bi0355995;
RA Miron S., Munier-Lehmann H., Craescu C.T.;
RT "Structural and dynamic studies on ligand-free adenylate kinase from
RT Mycobacterium tuberculosis revealed a closed conformation that can be
RT related to the reduced catalytic activity.";
RL Biochemistry 43:67-77(2004).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH ADP.
RX PubMed=16672241; DOI=10.1110/ps.062163406;
RA Bellinzoni M., Haouz A., Grana M., Munier-Lehmann H., Shepard W.,
RA Alzari P.M.;
RT "The crystal structure of Mycobacterium tuberculosis adenylate kinase in
RT complex with two molecules of ADP and Mg2+ supports an associative
RT mechanism for phosphoryl transfer.";
RL Protein Sci. 15:1489-1493(2006).
CC -!- FUNCTION: Catalyzes the reversible transfer of the terminal phosphate
CC group between ATP and AMP. Plays an important role in cellular energy
CC homeostasis and in adenine nucleotide metabolism. Has a broad
CC specificity for nucleoside triphosphates, being highly active with ATP
CC or dATP as phosphate donors, and less active with GTP or UTP.
CC {ECO:0000255|HAMAP-Rule:MF_00235, ECO:0000269|PubMed:10398370}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AMP + ATP = 2 ADP; Xref=Rhea:RHEA:12973, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:456215, ChEBI:CHEBI:456216; EC=2.7.4.3;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00235,
CC ECO:0000269|PubMed:10398370};
CC -!- ACTIVITY REGULATION: Competitively inhibited by the bisubstrate analog
CC Ap5A, by 7-deazaadenosine 5'-monophosphate (TuMP) and 8-bromo-AMP.
CC {ECO:0000269|PubMed:10398370}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=43 uM for ATP (at pH 7.4 and 30 degrees Celsius)
CC {ECO:0000269|PubMed:10398370};
CC KM=208 uM for AMP (at pH 7.4 and 30 degrees Celsius)
CC {ECO:0000269|PubMed:10398370};
CC KM=72 uM for ADP (at pH 7.4 and 30 degrees Celsius)
CC {ECO:0000269|PubMed:10398370};
CC Vmax=235 umol/min/mg enzyme for the forward reaction (at pH 7.4 and
CC 30 degrees Celsius) {ECO:0000269|PubMed:10398370};
CC Vmax=190 umol/min/mg enzyme for the reverse reaction (at pH 7.4 and
CC 30 degrees Celsius) {ECO:0000269|PubMed:10398370};
CC Temperature dependence:
CC Optimum temperature is 50-55 degrees Celsius. Highly thermostable. Is
CC half-inactivated at about 67 degrees Celsius.
CC {ECO:0000269|PubMed:10398370};
CC -!- PATHWAY: Purine metabolism; AMP biosynthesis via salvage pathway; AMP
CC from ADP: step 1/1. {ECO:0000255|HAMAP-Rule:MF_00235}.
CC -!- SUBUNIT: Monomer. {ECO:0000255|HAMAP-Rule:MF_00235}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00235}.
CC -!- DOMAIN: Consists of three domains, a large central CORE domain and two
CC small peripheral domains, NMPbind and LID, which undergo movements
CC during catalysis. The LID domain closes over the site of phosphoryl
CC transfer upon ATP binding. Assembling and dissambling the active center
CC during each catalytic cycle provides an effective means to prevent ATP
CC hydrolysis. The LID domain is a solvent-exposed domain that is much
CC shorter in Mycobacterium than in many other bacteria like E.coli.
CC {ECO:0000255|HAMAP-Rule:MF_00235, ECO:0000305|PubMed:14705932}.
CC -!- MASS SPECTROMETRY: Mass=20123.5; Mass_error=1.6; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:10398370};
CC -!- SIMILARITY: Belongs to the adenylate kinase family. {ECO:0000255|HAMAP-
CC Rule:MF_00235}.
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DR EMBL; AL123456; CCP43478.1; -; Genomic_DNA.
DR PIR; H70822; H70822.
DR RefSeq; NP_215247.1; NC_000962.3.
DR RefSeq; WP_003403726.1; NZ_NVQJ01000007.1.
DR PDB; 1P4S; NMR; -; A=1-181.
DR PDB; 2CDN; X-ray; 1.90 A; A=1-181.
DR PDBsum; 1P4S; -.
DR PDBsum; 2CDN; -.
DR AlphaFoldDB; P9WKF5; -.
DR SMR; P9WKF5; -.
DR STRING; 83332.Rv0733; -.
DR PaxDb; P9WKF5; -.
DR DNASU; 888567; -.
DR GeneID; 45424698; -.
DR GeneID; 888567; -.
DR KEGG; mtu:Rv0733; -.
DR TubercuList; Rv0733; -.
DR eggNOG; COG0563; Bacteria.
DR OMA; FHNRMRV; -.
DR PhylomeDB; P9WKF5; -.
DR BRENDA; 2.7.4.3; 3445.
DR UniPathway; UPA00588; UER00649.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0004017; F:adenylate kinase activity; IDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IDA:MTBBASE.
DR GO; GO:0004550; F:nucleoside diphosphate kinase activity; IDA:MTBBASE.
DR GO; GO:0044209; P:AMP salvage; IDA:MTBBASE.
DR GO; GO:0009132; P:nucleoside diphosphate metabolic process; IDA:MTBBASE.
DR GO; GO:0009123; P:nucleoside monophosphate metabolic process; IDA:MTBBASE.
DR GO; GO:0009141; P:nucleoside triphosphate metabolic process; IDA:MTBBASE.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0006144; P:purine nucleobase metabolic process; IDA:MTBBASE.
DR CDD; cd01428; ADK; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_00235; Adenylate_kinase_Adk; 1.
DR InterPro; IPR000850; Adenylat/UMP-CMP_kin.
DR InterPro; IPR033690; Adenylat_kinase_CS.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR23359; PTHR23359; 1.
DR PRINTS; PR00094; ADENYLTKNASE.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00113; ADENYLATE_KINASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cytoplasm; Direct protein sequencing;
KW Isopeptide bond; Kinase; Nucleotide biosynthesis; Nucleotide-binding;
KW Reference proteome; Transferase; Ubl conjugation.
FT CHAIN 1..181
FT /note="Adenylate kinase"
FT /id="PRO_0000158806"
FT REGION 30..59
FT /note="NMP"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00235,
FT ECO:0000269|PubMed:14705932"
FT REGION 126..132
FT /note="LID"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00235,
FT ECO:0000269|PubMed:14705932"
FT BINDING 10..15
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00235,
FT ECO:0000269|PubMed:16672241"
FT BINDING 31
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00235,
FT ECO:0000269|PubMed:16672241"
FT BINDING 36
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00235,
FT ECO:0000269|PubMed:16672241"
FT BINDING 57..59
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00235,
FT ECO:0000269|PubMed:16672241"
FT BINDING 85..88
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00235,
FT ECO:0000269|PubMed:16672241"
FT BINDING 92
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00235,
FT ECO:0000269|PubMed:16672241"
FT BINDING 127
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00235,
FT ECO:0000269|PubMed:16672241"
FT BINDING 129
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00235,
FT ECO:0000269|PubMed:16672241"
FT BINDING 140
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00235,
FT ECO:0000269|PubMed:16672241"
FT BINDING 166
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00235,
FT ECO:0000269|PubMed:16672241"
FT CROSSLNK 94
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-Cter in protein Pup)"
FT /evidence="ECO:0000269|PubMed:20066036"
FT STRAND 2..6
FT /evidence="ECO:0007829|PDB:2CDN"
FT STRAND 8..11
FT /evidence="ECO:0007829|PDB:1P4S"
FT HELIX 13..24
FT /evidence="ECO:0007829|PDB:2CDN"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:2CDN"
FT HELIX 31..40
FT /evidence="ECO:0007829|PDB:2CDN"
FT HELIX 44..55
FT /evidence="ECO:0007829|PDB:2CDN"
FT HELIX 61..71
FT /evidence="ECO:0007829|PDB:2CDN"
FT HELIX 75..77
FT /evidence="ECO:0007829|PDB:2CDN"
FT STRAND 81..85
FT /evidence="ECO:0007829|PDB:2CDN"
FT HELIX 90..102
FT /evidence="ECO:0007829|PDB:2CDN"
FT STRAND 109..114
FT /evidence="ECO:0007829|PDB:2CDN"
FT HELIX 117..127
FT /evidence="ECO:0007829|PDB:2CDN"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:1P4S"
FT HELIX 134..147
FT /evidence="ECO:0007829|PDB:2CDN"
FT TURN 148..150
FT /evidence="ECO:0007829|PDB:2CDN"
FT HELIX 151..154
FT /evidence="ECO:0007829|PDB:2CDN"
FT TURN 155..158
FT /evidence="ECO:0007829|PDB:2CDN"
FT STRAND 159..163
FT /evidence="ECO:0007829|PDB:2CDN"
FT HELIX 168..178
FT /evidence="ECO:0007829|PDB:2CDN"
SQ SEQUENCE 181 AA; 20125 MW; 8BF4829220AEEC52 CRC64;
MRVLLLGPPG AGKGTQAVKL AEKLGIPQIS TGELFRRNIE EGTKLGVEAK RYLDAGDLVP
SDLTNELVDD RLNNPDAANG FILDGYPRSV EQAKALHEML ERRGTDIDAV LEFRVSEEVL
LERLKGRGRA DDTDDVILNR MKVYRDETAP LLEYYRDQLK TVDAVGTMDE VFARALRALG
K
