KAMA_CLOSU
ID KAMA_CLOSU Reviewed; 416 AA.
AC Q9XBQ8;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=L-lysine 2,3-aminomutase;
DE Short=LAM;
DE EC=5.4.3.2;
DE AltName: Full=KAM;
GN Name=kamA;
OS Clostridium subterminale.
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Clostridiaceae;
OC Clostridium.
OX NCBI_TaxID=1550;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-16; 342-389 AND
RP 401-416, AND CHARACTERIZATION.
RC STRAIN=SB4;
RX PubMed=10629195; DOI=10.1128/jb.182.2.469-476.2000;
RA Ruzicka F.J., Lieder K.W., Frey P.A.;
RT "Lysine 2,3-aminomutase from Clostridium subterminale SB4: mass spectral
RT characterization of cyanogen bromide-treated peptides and cloning,
RT sequencing, and expression of the gene kamA in Escherichia coli.";
RL J. Bacteriol. 182:469-476(2000).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP ACTIVITY REGULATION.
RX PubMed=5438361; DOI=10.1016/s0021-9258(19)77160-9;
RA Chirpich T.P., Zappia V., Costilow R.N., Barker H.A.;
RT "Lysine 2,3-aminomutase. Purification and properties of a pyridoxal
RT phosphate and S-adenosylmethionine-activated enzyme.";
RL J. Biol. Chem. 245:1778-1789(1970).
RN [3]
RP SUBUNIT.
RC STRAIN=SB4;
RX PubMed=2019591; DOI=10.1016/s0021-9258(20)89497-6;
RA Song K.B., Frey P.A.;
RT "Molecular properties of lysine-2,3-aminomutase.";
RL J. Biol. Chem. 266:7651-7655(1991).
RN [4]
RP FUNCTION, COFACTOR, AND ACTIVITY REGULATION.
RX PubMed=1850415; DOI=10.1016/s0021-9258(20)89498-8;
RA Petrovich R.M., Ruzicka F.J., Reed G.H., Frey P.A.;
RT "Metal cofactors of lysine-2,3-aminomutase.";
RL J. Biol. Chem. 266:7656-7660(1991).
RN [5]
RP FUNCTION, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=1329954; DOI=10.1021/bi00159a019;
RA Petrovich R.M., Ruzicka F.J., Reed G.H., Frey P.A.;
RT "Characterization of iron-sulfur clusters in lysine 2,3-aminomutase by
RT electron paramagnetic resonance spectroscopy.";
RL Biochemistry 31:10774-10781(1992).
RN [6]
RP ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11370852; DOI=10.1006/abbi.2001.2261;
RA Miller J., Bandarian V., Reed G.H., Frey P.A.;
RT "Inhibition of lysine 2,3-aminomutase by the alternative substrate 4-
RT thialysine and characterization of the 4-thialysyl radical intermediate.";
RL Arch. Biochem. Biophys. 387:281-288(2001).
RN [7]
RP MUTAGENESIS OF GLU-86; ASP-96; ARG-130; ARG-134; ARG-135; ARG-136; ASP-165;
RP ASP-172; GLU-236; ASP-293 AND ASP-330.
RX PubMed=17042481; DOI=10.1021/bi061329l;
RA Chen D., Frey P.A., Lepore B.W., Ringe D., Ruzicka F.J.;
RT "Identification of structural and catalytic classes of highly conserved
RT amino acid residues in lysine 2,3-aminomutase.";
RL Biochemistry 45:12647-12653(2006).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH SUBSTRATE AND
RP COFACTOR.
RC STRAIN=SB4;
RX PubMed=16166264; DOI=10.1073/pnas.0505726102;
RA Lepore B.W., Ruzicka F.J., Frey P.A., Ringe D.;
RT "The X-ray crystal structure of lysine-2,3-aminomutase from Clostridium
RT subterminale.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:13819-13824(2005).
CC -!- FUNCTION: Catalyzes the interconversion of L-alpha-lysine and L-beta-
CC lysine. {ECO:0000269|PubMed:1329954, ECO:0000269|PubMed:1850415,
CC ECO:0000269|PubMed:5438361}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysine = (3S)-3,6-diaminohexanoate; Xref=Rhea:RHEA:19177,
CC ChEBI:CHEBI:32551, ChEBI:CHEBI:57434; EC=5.4.3.2;
CC Evidence={ECO:0000269|PubMed:5438361};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Note=Binds 1 [4Fe-4S] cluster per subunit. The cluster is coordinated
CC with 3 cysteines and an exchangeable S-adenosyl-L-methionine.;
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC -!- COFACTOR:
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Note=Binds 1 Co(2+) ion per subunit.;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Note=Binds 1 zinc ion per subunit.;
CC -!- ACTIVITY REGULATION: The enzyme is activated by S-adenosyl-methionine.
CC Activity is dependent on the levels of Fe(2+), S(2-) and Co(2+).
CC Activity is stimulated by addition of EDTA. S-adenosylhomocysteine
CC competitively inhibits the activity whereas 5'-methylthioadenosine is
CC not inhibitory in the presence of S-adenosylmethionine. Competitively
CC inhibited by 4-thialysine. Inhibited by sodium borohydride (1 mM) when
CC added with 2 mM dithionate. Moderately inhibited by beta-
CC mercaptoethanol (30 mM) along with dithionate. Higher concentrations of
CC Fe(2+) partially inhibit the activity and Co(2+) at 1 mM is a strong
CC inhibitor. Hydroxylamine, isonicotinic acid hydrazide inhibit
CC effectively, in addition, hydrazine, D-penicillamine and D-cycloserine
CC are also inhibitory at high concentrations.
CC {ECO:0000269|PubMed:11370852, ECO:0000269|PubMed:1850415,
CC ECO:0000269|PubMed:5438361}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.6 uM for L-lysine {ECO:0000269|PubMed:11370852,
CC ECO:0000269|PubMed:1329954, ECO:0000269|PubMed:5438361};
CC KM=28 nM for adenosylmethionine {ECO:0000269|PubMed:11370852,
CC ECO:0000269|PubMed:1329954, ECO:0000269|PubMed:5438361};
CC KM=1.4 mM for 4-thialysine {ECO:0000269|PubMed:11370852,
CC ECO:0000269|PubMed:1329954, ECO:0000269|PubMed:5438361};
CC Vmax=0.19 umol/min/mg enzyme with 4-thialysine as substrate (at 37
CC degrees Celsius and pH 8) {ECO:0000269|PubMed:11370852,
CC ECO:0000269|PubMed:1329954, ECO:0000269|PubMed:5438361};
CC pH dependence:
CC Optimum pH is 8.0. Displays half maximal activity between pH 6.0 and
CC 9.8. {ECO:0000269|PubMed:11370852, ECO:0000269|PubMed:1329954,
CC ECO:0000269|PubMed:5438361};
CC Redox potential:
CC E(0) is between -336 and -370 mV for 4Fe-4S cluster.
CC {ECO:0000269|PubMed:11370852, ECO:0000269|PubMed:1329954,
CC ECO:0000269|PubMed:5438361};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius. It has strong activity at
CC 37 degrees Celsius but is reversibly inactivated in temperatures
CC between 37 and 65 degrees Celsius. Minimal loss of activity is
CC observed in enzyme stored at -10 degrees Celsius in the presence of
CC 15% glycerol. {ECO:0000269|PubMed:11370852,
CC ECO:0000269|PubMed:1329954, ECO:0000269|PubMed:5438361};
CC -!- PATHWAY: Amino-acid degradation; L-lysine degradation via acetate
CC pathway.
CC -!- SUBUNIT: Homohexamer; trimer of dimers. Forms a homotetramer in
CC crystal. {ECO:0000269|PubMed:16166264, ECO:0000269|PubMed:2019591}.
CC -!- SIMILARITY: Belongs to the radical SAM superfamily. KamA family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF159146; AAD43134.1; -; Genomic_DNA.
DR PDB; 2A5H; X-ray; 2.10 A; A/B/C/D=1-416.
DR PDBsum; 2A5H; -.
DR AlphaFoldDB; Q9XBQ8; -.
DR SMR; Q9XBQ8; -.
DR BioCyc; MetaCyc:MON-12270; -.
DR BRENDA; 5.4.3.2; 1523.
DR UniPathway; UPA00870; -.
DR EvolutionaryTrace; Q9XBQ8; -.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0050066; F:lysine 2,3-aminomutase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019475; P:L-lysine catabolic process to acetate; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR025895; LAM_C_dom.
DR InterPro; IPR003739; Lys_aminomutase/Glu_NH3_mut.
DR InterPro; IPR022459; Lysine_aminomutase.
DR InterPro; IPR007197; rSAM.
DR PANTHER; PTHR30538; PTHR30538; 1.
DR Pfam; PF12544; LAM_C; 1.
DR Pfam; PF04055; Radical_SAM; 1.
DR PIRSF; PIRSF004911; DUF160; 1.
DR SFLD; SFLDF00283; L-lysine_2_3-aminomutase_(LAM; 1.
DR SFLD; SFLDG01070; PLP-dependent; 1.
DR TIGRFAMs; TIGR03820; lys_2_3_AblA; 1.
DR TIGRFAMs; TIGR00238; TIGR00238; 1.
DR PROSITE; PS51918; RADICAL_SAM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; Cobalt; Direct protein sequencing; Iron; Iron-sulfur;
KW Isomerase; Metal-binding; Pyridoxal phosphate; S-adenosyl-L-methionine;
KW Zinc.
FT CHAIN 1..416
FT /note="L-lysine 2,3-aminomutase"
FT /id="PRO_0000172287"
FT DOMAIN 111..322
FT /note="Radical SAM core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT BINDING 125
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT BINDING 129
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT BINDING 132
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT BINDING 268
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 375
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 377
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 380
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT MOD_RES 337
FT /note="N6-(pyridoxal phosphate)lysine"
FT MUTAGEN 86
FT /note="E->Q: Reduction in activity. Decrease in iron and
FT sulfide and PLP content."
FT /evidence="ECO:0000269|PubMed:17042481"
FT MUTAGEN 96
FT /note="D->N: Reduction in activity. Decrease in iron and
FT sulfide and PLP content."
FT /evidence="ECO:0000269|PubMed:17042481"
FT MUTAGEN 130
FT /note="R->Q,K: Complete loss of activity. Decrease in iron
FT and sulfide but not PLP content. Destabilise the iron-
FT sulfur centers."
FT /evidence="ECO:0000269|PubMed:17042481"
FT MUTAGEN 134
FT /note="R->K: Complete loss of activity. Significant
FT decrease in iron and sulfide and PLP content."
FT /evidence="ECO:0000269|PubMed:17042481"
FT MUTAGEN 134
FT /note="R->Q: Complete loss of activity. Slight decrease in
FT iron and sulfide and PLP content."
FT /evidence="ECO:0000269|PubMed:17042481"
FT MUTAGEN 135
FT /note="R->K: Reduction in activity. Decrease in iron and
FT sulfide and PLP content."
FT /evidence="ECO:0000269|PubMed:17042481"
FT MUTAGEN 135
FT /note="R->Q: Reduction in activity. Significant decrease in
FT iron and sulfide and PLP content."
FT /evidence="ECO:0000269|PubMed:17042481"
FT MUTAGEN 136
FT /note="R->Q: Reduction in activity. Significant decrease in
FT iron and sulfide and PLP content."
FT /evidence="ECO:0000269|PubMed:17042481"
FT MUTAGEN 165
FT /note="D->N: Significant reduction in activity. Decrease in
FT iron and sulfide and PLP content."
FT /evidence="ECO:0000269|PubMed:17042481"
FT MUTAGEN 172
FT /note="D->N: Complete loss of activity. Decrease in iron
FT and sulfide and PLP content. Destabilise the iron-sulfur
FT centers."
FT /evidence="ECO:0000269|PubMed:17042481"
FT MUTAGEN 236
FT /note="E->Q: Significant reduction in activity. Decrease in
FT iron and sulfide and PLP content."
FT /evidence="ECO:0000269|PubMed:17042481"
FT MUTAGEN 293
FT /note="D->N: Complete loss of activity. Decrease in iron
FT and sulfide and PLP content."
FT /evidence="ECO:0000269|PubMed:17042481"
FT MUTAGEN 330
FT /note="D->A,N: Complete loss of activity. Decrease in iron
FT and sulfide and PLP content."
FT /evidence="ECO:0000269|PubMed:17042481"
FT HELIX 4..8
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 14..17
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 20..25
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 31..35
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 42..49
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 61..64
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 75..80
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 84..87
FT /evidence="ECO:0007829|PDB:2A5H"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:2A5H"
FT TURN 100..102
FT /evidence="ECO:0007829|PDB:2A5H"
FT STRAND 113..123
FT /evidence="ECO:0007829|PDB:2A5H"
FT TURN 133..139
FT /evidence="ECO:0007829|PDB:2A5H"
FT STRAND 140..144
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 147..158
FT /evidence="ECO:0007829|PDB:2A5H"
FT STRAND 165..171
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 178..189
FT /evidence="ECO:0007829|PDB:2A5H"
FT STRAND 196..200
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 203..206
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 208..210
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 213..219
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:2A5H"
FT STRAND 224..229
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 234..236
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 239..250
FT /evidence="ECO:0007829|PDB:2A5H"
FT STRAND 255..260
FT /evidence="ECO:0007829|PDB:2A5H"
FT TURN 263..265
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 269..281
FT /evidence="ECO:0007829|PDB:2A5H"
FT STRAND 284..290
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 299..301
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 305..313
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 321..323
FT /evidence="ECO:0007829|PDB:2A5H"
FT STRAND 326..331
FT /evidence="ECO:0007829|PDB:2A5H"
FT TURN 332..335
FT /evidence="ECO:0007829|PDB:2A5H"
FT STRAND 336..339
FT /evidence="ECO:0007829|PDB:2A5H"
FT STRAND 345..349
FT /evidence="ECO:0007829|PDB:2A5H"
FT STRAND 352..356
FT /evidence="ECO:0007829|PDB:2A5H"
FT STRAND 362..366
FT /evidence="ECO:0007829|PDB:2A5H"
FT TURN 378..382
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 390..395
FT /evidence="ECO:0007829|PDB:2A5H"
FT STRAND 400..402
FT /evidence="ECO:0007829|PDB:2A5H"
FT HELIX 408..410
FT /evidence="ECO:0007829|PDB:2A5H"
SQ SEQUENCE 416 AA; 47102 MW; 6C3602E5B87E25A1 CRC64;
MINRRYELFK DVSDADWNDW RWQVRNRIET VEELKKYIPL TKEEEEGVAQ CVKSLRMAIT
PYYLSLIDPN DPNDPVRKQA IPTALELNKA AADLEDPLHE DTDSPVPGLT HRYPDRVLLL
ITDMCSMYCR HCTRRRFAGQ SDDSMPMERI DKAIDYIRNT PQVRDVLLSG GDALLVSDET
LEYIIAKLRE IPHVEIVRIG SRTPVVLPQR ITPELVNMLK KYHPVWLNTH FNHPNEITEE
STRACQLLAD AGVPLGNQSV LLRGVNDCVH VMKELVNKLV KIRVRPYYIY QCDLSLGLEH
FRTPVSKGIE IIEGLRGHTS GYCVPTFVVD APGGGGKTPV MPNYVISQSH DKVILRNFEG
VITTYSEPIN YTPGCNCDVC TGKKKVHKVG VAGLLNGEGM ALEPVGLERN KRHVQE
