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Protein

Leucine dehydrogenase

Gene

ldh

Organism
Geobacillus stearothermophilus (Bacillus stearothermophilus)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the reversible deamination of L-leucine to 4-methyl-2-oxopentanoate.1 Publication

Catalytic activityi

L-leucine + H2O + NAD+ = 4-methyl-2-oxopentanoate + NH3 + NADH.1 Publication

Pathwayi: L-leucine degradation

This protein is involved in step 1 of the subpathway that synthesizes 4-methyl-2-oxopentanoate from L-leucine (dehydrogenase route).
Proteins known to be involved in this subpathway in this organism are:
  1. Leucine dehydrogenase (ldh)
This subpathway is part of the pathway L-leucine degradation, which is itself part of Amino-acid degradation.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes 4-methyl-2-oxopentanoate from L-leucine (dehydrogenase route), the pathway L-leucine degradation and in Amino-acid degradation.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei80 – 801PROSITE-ProRule annotation1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi180 – 1867NADSequence analysis

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Branched-chain amino acid catabolism

Keywords - Ligandi

NAD

Enzyme and pathway databases

BRENDAi1.4.1.9. 623.
UniPathwayiUPA00363; UER00858.

Names & Taxonomyi

Protein namesi
Recommended name:
Leucine dehydrogenase (EC:1.4.1.9)
Short name:
LeuDH
Gene namesi
Name:ldh
Synonyms:leuDH
OrganismiGeobacillus stearothermophilus (Bacillus stearothermophilus)
Taxonomic identifieri1422 [NCBI]
Taxonomic lineageiBacteriaFirmicutesBacilliBacillalesBacillaceaeGeobacillus

Pathology & Biotechi

Biotechnological usei

This enzyme has been successfully altered through several rounds of protein engineering to an enantioselective amine dehydrogenase. Instead of the wild-type alpha-keto acid, the new amine dehydrogenase now accepts the analogous ketone, methyl isobutyl ketone (MIBK), which corresponds to exchange of the carboxy group by a methyl group, to produce chiral (R)-1,3-dimethylbutylamine via a reductive amination reaction. This represents a suitable enzymatic production route for the asymmetric synthesis of amines from prochiral ketones and free ammonia, which is one of the top aspirational reactions challenging the pharmaceutical industry.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi68 – 681K → S: Completely modifies the activity of the enzyme, which is able to catalyze the reductive amination of ketones, and no longer diplays leucine dehydrogenase activity; when associated with V-114, C-261 and C-291. 1 Publication
Mutagenesisi114 – 1141E → V: Completely modifies the activity of the enzyme, which is able to catalyze the reductive amination of ketones, and no longer diplays leucine dehydrogenase activity; when associated with S-68, C-261 and C-291. 1 Publication
Mutagenesisi261 – 2611D → C: Completely modifies the activity of the enzyme, which is able to catalyze the reductive amination of ketones, and no longer diplays leucine dehydrogenase activity; when associated with S-68, V-114 and C-291. 1 Publication
Mutagenesisi291 – 2911V → C: Completely modifies the activity of the enzyme, which is able to catalyze the reductive amination of ketones, and no longer diplays leucine dehydrogenase activity; when associated with S-68, V-114 and C-261. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 367367Leucine dehydrogenasePRO_0000182803Add
BLAST

Interactioni

Subunit structurei

Homohexamer.1 Publication

Structurei

3D structure databases

ProteinModelPortaliP13154.
SMRiP13154. Positions 1-364.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR006095. Glu/Leu/Phe/Val_DH.
IPR006096. Glu/Leu/Phe/Val_DH_C.
IPR006097. Glu/Leu/Phe/Val_DH_dimer_dom.
IPR016211. Glu/Phe/Leu/Val_DH_bac/arc.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PANTHERiPTHR11606:SF3. PTHR11606:SF3. 1 hit.
PfamiPF00208. ELFV_dehydrog. 2 hits.
PF02812. ELFV_dehydrog_N. 1 hit.
[Graphical view]
PIRSFiPIRSF000188. Phe_leu_dh. 1 hit.
PRINTSiPR00082. GLFDHDRGNASE.
SMARTiSM00839. ELFV_dehydrog. 1 hit.
[Graphical view]
SUPFAMiSSF51735. SSF51735. 1 hit.
PROSITEiPS00074. GLFV_DEHYDROGENASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P13154-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MELFKYMETY DYEQVLFCQD KESGLKAIIA IHDTTLGPAL GGTRMWMYNS
60 70 80 90 100
EEEALEDALR LARGMTYKNA AAGLNLGGGK TVIIGDPRKD KNEAMFRAFG
110 120 130 140 150
RFIQGLNGRY ITAEDVGTTV ADMDIIYQET DYVTGISPEF GSSGNPSPAT
160 170 180 190 200
AYGVYRGMKA AAKEAFGSDS LEGKVVAVQG VGNVAYHLCR HLHEEGAKLI
210 220 230 240 250
VTDINKEVVA RAVEEFGAKA VDPNDIYGVE CDIFAPCALG GIINDQTIPQ
260 270 280 290 300
LKAKVIAGSA DNQLKEPRHG DIIHEMGIVY APDYVINAGG VINVADELYG
310 320 330 340 350
YNRERAMKKI EQIYDNIEKV FAIAKRDNIP TYVAADRMAE ERIETMRKAR
360
SPFLQNGHHI LSRRRAR
Length:367
Mass (Da):40,458
Last modified:October 25, 2004 - v3
Checksum:iE01E7086453D33DD
GO

Sequence cautioni

The sequence AAA22570.1 differs from that shown. Reason: Frameshift at position 365. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti350 – 3523RSP → ASQ in AAA22570 (PubMed:3069133).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M22977 Genomic DNA. Translation: AAA22570.1. Frameshift.
AB103384 Genomic DNA. Translation: BAC81829.1.
PIRiA31950.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M22977 Genomic DNA. Translation: AAA22570.1. Frameshift.
AB103384 Genomic DNA. Translation: BAC81829.1.
PIRiA31950.

3D structure databases

ProteinModelPortaliP13154.
SMRiP13154. Positions 1-364.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

UniPathwayiUPA00363; UER00858.
BRENDAi1.4.1.9. 623.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR006095. Glu/Leu/Phe/Val_DH.
IPR006096. Glu/Leu/Phe/Val_DH_C.
IPR006097. Glu/Leu/Phe/Val_DH_dimer_dom.
IPR016211. Glu/Phe/Leu/Val_DH_bac/arc.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PANTHERiPTHR11606:SF3. PTHR11606:SF3. 1 hit.
PfamiPF00208. ELFV_dehydrog. 2 hits.
PF02812. ELFV_dehydrog_N. 1 hit.
[Graphical view]
PIRSFiPIRSF000188. Phe_leu_dh. 1 hit.
PRINTSiPR00082. GLFDHDRGNASE.
SMARTiSM00839. ELFV_dehydrog. 1 hit.
[Graphical view]
SUPFAMiSSF51735. SSF51735. 1 hit.
PROSITEiPS00074. GLFV_DEHYDROGENASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Gene cloning and sequence determination of leucine dehydrogenase from Bacillus stearothermophilus and structural comparison with other NAD(P)+-dependent dehydrogenases."
    Nagata S., Tanizawa K., Esaki N., Sakamoto Y., Ohshima T., Tanaka H., Soda K.
    Biochemistry 27:9056-9062(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT.
    Strain: ATCC 12980 / DSM 22 / JCM 2501 / NBRC 12550 / NCIMB 8923 / NCTC 10339 / VKM B-510.
  2. "Nucleotide sequence, cloning, overexpression and site-directed mutagenesis of the leucine dehydrogenase gene from Bacillus sphaericus."
    Katoh R., Seki M., Nagata S., Misono H.
    Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Leucine dehydrogenase from Bacillus stearothermophilus: identification of active-site lysine by modification with pyridoxal phosphate."
    Matsuyama T., Soda K., Fukui T., Tanizawa K.
    J. Biochem. 112:258-265(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACTIVE SITE LYS-80.
  4. Cited for: MUTAGENESIS OF LYS-68; GLU-114; ASP-261 AND VAL-291, BIOTECHNOLOGY.

Entry informationi

Entry nameiDHLE_GEOSE
AccessioniPrimary (citable) accession number: P13154
Secondary accession number(s): Q76GN7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: October 25, 2004
Last modified: December 9, 2015
This is version 96 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Direct protein sequencing

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.