PRODH_THET2
ID PRODH_THET2 Reviewed; 307 AA.
AC Q72IB8;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Proline dehydrogenase {ECO:0000303|PubMed:17344208};
DE Short=PRODH {ECO:0000303|PubMed:17344208};
DE EC=1.5.5.2 {ECO:0000269|PubMed:17344208, ECO:0000269|PubMed:18426222};
DE AltName: Full=Proline oxidase {ECO:0000305};
DE AltName: Full=TtPRODH {ECO:0000303|PubMed:17344208};
GN OrderedLocusNames=TT_C1214 {ECO:0000312|EMBL:AAS81556.1};
OS Thermus thermophilus (strain ATCC BAA-163 / DSM 7039 / HB27).
OC Bacteria; Deinococcus-Thermus; Deinococci; Thermales; Thermaceae; Thermus.
OX NCBI_TaxID=262724 {ECO:0000312|EMBL:AAS81556.1};
RN [1] {ECO:0000312|EMBL:AAS81556.1, ECO:0000312|Proteomes:UP000000592}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-163 / DSM 7039 / HB27 {ECO:0000312|Proteomes:UP000000592};
RX PubMed=15064768; DOI=10.1038/nbt956;
RA Henne A., Brueggemann H., Raasch C., Wiezer A., Hartsch T., Liesegang H.,
RA Johann A., Lienard T., Gohl O., Martinez-Arias R., Jacobi C.,
RA Starkuviene V., Schlenczeck S., Dencker S., Huber R., Klenk H.-P.,
RA Kramer W., Merkl R., Gottschalk G., Fritz H.-J.;
RT "The genome sequence of the extreme thermophile Thermus thermophilus.";
RL Nat. Biotechnol. 22:547-553(2004).
RN [2] {ECO:0007744|PDB:2G37}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH FAD, FUNCTION,
RP CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, AND PHYLOGENETIC STUDY.
RX PubMed=17344208; DOI=10.1074/jbc.m700912200;
RA White T.A., Krishnan N., Becker D.F., Tanner J.J.;
RT "Structure and kinetics of monofunctional proline dehydrogenase from
RT Thermus thermophilus.";
RL J. Biol. Chem. 282:14316-14327(2007).
RN [3] {ECO:0007744|PDB:2EKG}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF INACTIVE ENZYME IN COMPLEX WITH
RP FAD, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, AND MASS
RP SPECTROMETRY.
RX PubMed=18426222; DOI=10.1021/bi800055w;
RA White T.A., Johnson W.H., Whitman C.P., Tanner J.J.;
RT "Structural basis for the inactivation of Thermus thermophilus proline
RT dehydrogenase by N-propargylglycine.";
RL Biochemistry 47:5573-5580(2008).
CC -!- FUNCTION: Converts proline to delta-1-pyrroline-5-carboxylate
CC (PubMed:17344208, PubMed:18426222). Has significant activity against
CC O(2) producing superoxide during proline oxidation catalytic cycle
CC (PubMed:17344208). {ECO:0000269|PubMed:17344208,
CC ECO:0000269|PubMed:18426222}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a quinone + L-proline = (S)-1-pyrroline-5-carboxylate + a
CC quinol + H(+); Xref=Rhea:RHEA:23784, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17388, ChEBI:CHEBI:24646, ChEBI:CHEBI:60039,
CC ChEBI:CHEBI:132124; EC=1.5.5.2;
CC Evidence={ECO:0000269|PubMed:17344208, ECO:0000269|PubMed:18426222};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:17344208, ECO:0000269|PubMed:18426222};
CC Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:17344208};
CC -!- ACTIVITY REGULATION: Inhibited by L-tetrahydro-2-furoic acid (THFA), L-
CC mandelate and L-lactate (PubMed:17344208). Inhibited by N-
CC propargylglycine (PubMed:18426222). {ECO:0000269|PubMed:18426222}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=27 mM for L-proline (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:17344208};
CC KM=4 mM for 3,4-dehydro-L-proline (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:17344208};
CC Vmax=20.5 umol/min/mg enzyme for L-proline (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:17344208};
CC Vmax=119 umol/min/mg enzyme for 3,4-dehydro-L-proline (at 25 degrees
CC Celsius) {ECO:0000269|PubMed:17344208};
CC Note=kcat is 13 sec(-1) for L-proline. kcat is 75 sec(-1) for 3,4-
CC dehydro-L-proline. {ECO:0000269|PubMed:17344208};
CC Redox potential:
CC E(0) is -75 mV. {ECO:0000269|PubMed:17344208};
CC Temperature dependence:
CC Highly thermostable. Exhibits over 85% or 60% of activity after a 1
CC hour or 3 hours incubation at 90 degrees Celsius, respectively. The
CC half-life is estimated to be 257 minutes.
CC {ECO:0000269|PubMed:17344208};
CC -!- PATHWAY: Amino-acid degradation; L-proline degradation into L-
CC glutamate; L-glutamate from L-proline: step 1/2.
CC {ECO:0000305|PubMed:17344208}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17344208}.
CC -!- MASS SPECTROMETRY: Mass=37981; Method=Electrospray; Note=The measured
CC mass is that of native enzyme without the flavin.;
CC Evidence={ECO:0000269|PubMed:18426222};
CC -!- SIMILARITY: Belongs to the proline dehydrogenase family. {ECO:0000305}.
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DR EMBL; AE017221; AAS81556.1; -; Genomic_DNA.
DR RefSeq; WP_011173620.1; NC_005835.1.
DR PDB; 2EKG; X-ray; 1.90 A; A/B=1-307.
DR PDB; 2G37; X-ray; 2.00 A; A/B=1-307.
DR PDBsum; 2EKG; -.
DR PDBsum; 2G37; -.
DR AlphaFoldDB; Q72IB8; -.
DR SMR; Q72IB8; -.
DR STRING; 262724.TT_C1214; -.
DR EnsemblBacteria; AAS81556; AAS81556; TT_C1214.
DR KEGG; tth:TT_C1214; -.
DR eggNOG; COG0506; Bacteria.
DR HOGENOM; CLU_061158_0_0_0; -.
DR OMA; YPMIGSH; -.
DR OrthoDB; 1746057at2; -.
DR BRENDA; 1.5.5.2; 2305.
DR BRENDA; 1.5.99.B2; 2305.
DR UniPathway; UPA00261; UER00373.
DR EvolutionaryTrace; Q72IB8; -.
DR Proteomes; UP000000592; Chromosome.
DR GO; GO:0071949; F:FAD binding; IDA:UniProtKB.
DR GO; GO:0004657; F:proline dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0006562; P:proline catabolic process; IDA:UniProtKB.
DR GO; GO:0010133; P:proline catabolic process to glutamate; IEA:UniProtKB-UniPathway.
DR InterPro; IPR029041; FAD-linked_oxidoreductase-like.
DR InterPro; IPR008219; PRODH_bac_arc.
DR InterPro; IPR002872; Proline_DH_dom.
DR InterPro; IPR015659; Proline_oxidase.
DR PANTHER; PTHR13914; PTHR13914; 2.
DR Pfam; PF01619; Pro_dh; 1.
DR PIRSF; PIRSF000196; Pro_dehydrog; 1.
DR SUPFAM; SSF51730; SSF51730; 1.
PE 1: Evidence at protein level;
KW 3D-structure; FAD; Flavoprotein; Nucleotide-binding; Oxidoreductase;
KW Proline metabolism.
FT CHAIN 1..307
FT /note="Proline dehydrogenase"
FT /id="PRO_0000436837"
FT ACT_SITE 133
FT /evidence="ECO:0000305|PubMed:18426222"
FT ACT_SITE 184
FT /evidence="ECO:0000305|PubMed:18426222"
FT BINDING 99
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9RW55"
FT BINDING 134
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17344208,
FT ECO:0000269|PubMed:18426222, ECO:0007744|PDB:2EKG,
FT ECO:0007744|PDB:2G37"
FT BINDING 163
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17344208,
FT ECO:0000269|PubMed:18426222, ECO:0007744|PDB:2EKG,
FT ECO:0007744|PDB:2G37"
FT BINDING 187..189
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17344208,
FT ECO:0000269|PubMed:18426222, ECO:0007744|PDB:2EKG,
FT ECO:0007744|PDB:2G37"
FT BINDING 201
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17344208,
FT ECO:0007744|PDB:2G37"
FT BINDING 226..227
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17344208,
FT ECO:0000269|PubMed:18426222, ECO:0007744|PDB:2EKG,
FT ECO:0007744|PDB:2G37"
FT BINDING 288..289
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9RW55"
FT SITE 275
FT /note="Critical for catalytic activity"
FT /evidence="ECO:0000305|PubMed:18426222"
FT HELIX 6..15
FT /evidence="ECO:0007829|PDB:2EKG"
FT HELIX 18..27
FT /evidence="ECO:0007829|PDB:2EKG"
FT HELIX 29..35
FT /evidence="ECO:0007829|PDB:2EKG"
FT HELIX 41..53
FT /evidence="ECO:0007829|PDB:2EKG"
FT STRAND 57..63
FT /evidence="ECO:0007829|PDB:2EKG"
FT HELIX 70..87
FT /evidence="ECO:0007829|PDB:2EKG"
FT STRAND 94..100
FT /evidence="ECO:0007829|PDB:2EKG"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:2EKG"
FT TURN 104..107
FT /evidence="ECO:0007829|PDB:2EKG"
FT HELIX 109..123
FT /evidence="ECO:0007829|PDB:2EKG"
FT HELIX 124..126
FT /evidence="ECO:0007829|PDB:2EKG"
FT STRAND 128..132
FT /evidence="ECO:0007829|PDB:2EKG"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:2EKG"
FT HELIX 140..152
FT /evidence="ECO:0007829|PDB:2EKG"
FT STRAND 157..163
FT /evidence="ECO:0007829|PDB:2EKG"
FT HELIX 169..176
FT /evidence="ECO:0007829|PDB:2EKG"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:2EKG"
FT STRAND 183..186
FT /evidence="ECO:0007829|PDB:2EKG"
FT TURN 194..196
FT /evidence="ECO:0007829|PDB:2EKG"
FT HELIX 201..217
FT /evidence="ECO:0007829|PDB:2EKG"
FT STRAND 222..225
FT /evidence="ECO:0007829|PDB:2EKG"
FT HELIX 229..241
FT /evidence="ECO:0007829|PDB:2EKG"
FT HELIX 246..248
FT /evidence="ECO:0007829|PDB:2EKG"
FT STRAND 249..254
FT /evidence="ECO:0007829|PDB:2EKG"
FT HELIX 259..267
FT /evidence="ECO:0007829|PDB:2EKG"
FT STRAND 271..279
FT /evidence="ECO:0007829|PDB:2EKG"
FT HELIX 282..292
FT /evidence="ECO:0007829|PDB:2EKG"
SQ SEQUENCE 307 AA; 35492 MW; FAF48017D95B3EDD CRC64;
MNLDLAYRSF VLGVAGHPQV ERLIKHRAKG LVRRYVAGET LEEALKAAEA LEREGVHAIL
DLLGEMVRTE EEARAFQRGL LELVWALAGK PWPKYISLKL TQLGLDLSED LALALLREVL
REAEPRGVFV RLDMEDSPRV EATLRLYRAL REEGFSQVGI VLQSYLYRTE KDLLDLLPYR
PNLRLVKGAY REPKEVAFPD KRLIDAEYLH LGKLALKEGL YVAFATHDPR IIAELKRYTE
AMGIPRSRFE FQFLYGVRPE EQRRLAREGY TVRAYVPYGR DWYPYLTRRI AERPENLLLV
LRSLVSG
