4-hydroxy-tetrahydrodipicolinate reductase - Escherichia coli (strain K12)

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P04036 (DAPB_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 131. History...

Clusters with 100%, 90%, 50% identity |

Documents (4) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
4-hydroxy-tetrahydrodipicolinate reductase
Short name=HTPA reductase
EC=1.17.1.8

Gene names

Name:	dapB
Ordered Locus Names:	b0031, JW0029

Organism

Escherichia coli (strain K12) [Reference proteome] [HAMAP]

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia ›

Protein attributes

Sequence length	273 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the conversion of 4-hydroxy-tetrahydrodipicolinate (HTPA) to tetrahydrodipicolinate. Can use both NADH and NADPH as a reductant, with NADH being twice as effective as NADPH. Ref.6 Ref.8
Catalytic activity	(S)-2,3,4,5-tetrahydropyridine-2,6-dicarboxylate + NAD(P)⁺ + H₂O = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + NAD(P)H. Ref.8
Enzyme regulation	Is inhibited by 2,6-pyridine dicarboxylate (2,6-PDC or picolinate). Ref.11
Pathway	Amino-acid biosynthesis; L-lysine biosynthesis via DAP pathway; (S)-tetrahydrodipicolinate from L-aspartate: step 4/4. HAMAP-Rule MF_00102
Subunit structure	Homotetramer. Ref.6
Subcellular location	Cytoplasm HAMAP-Rule MF_00102.
Induction	Expression of dapB is up-regulated by ArgP and is repressed by lysine that prevents the binding of the ArgP activator. Thus, ArgP contributes to enhanced transcription of dapB when lysine becomes limiting. Ref.7 Ref.11
Sequence similarities	Belongs to the DapB family.
Caution	Was originally thought to be a dihydrodipicolinate reductase (DHDPR), catalyzing the conversion of dihydrodipicolinate to tetrahydrodipicolinate. However, it was shown (Ref.8) that the substrate of the enzymatic reaction is not dihydrodipicolinate (DHDP) but in fact (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid (HTPA), the product released by the DapA-catalyzed reaction.
Biophysicochemical properties	Kinetic parameters: K_M=1.6 µM for NADH Ref.6 Ref.11 K_M=8 µM for NADPH
Mass spectrometry	Molecular mass is 28758±8 Da from positions 1 - 273. Determined by ESI. Ref.6

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Diaminopimelate biosynthesis Lysine biosynthesis
Cellular component	Cytoplasm
Ligand	NAD NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	diaminopimelate biosynthetic process Inferred from direct assay PubMed 4151489. Source: EcoliWiki lysine biosynthetic process via diaminopimelate Inferred from electronic annotation. Source: HAMAP
Cellular_component	cytosol Inferred from direct assay PubMed 16858726. Source: UniProtKB
Molecular_function	4-hydroxy-tetrahydrodipicolinate reductase Inferred from electronic annotation. Source: InterPro NAD binding Inferred from electronic annotation. Source: HAMAP NADPH binding Inferred from electronic annotation. Source: InterPro oxidoreductase activity, acting on CH or CH2 groups, NAD or NADP as acceptor Inferred from electronic annotation. Source: HAMAP
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 273

273

4-hydroxy-tetrahydrodipicolinate reductase HAMAP-Rule MF_00102

PRO_0000141437

Regions

Nucleotide binding

12 – 17

NAD(P) HAMAP-Rule MF_00102

Nucleotide binding

102 – 104

NAD(P) HAMAP-Rule MF_00102

Nucleotide binding

126 – 129

NAD(P) HAMAP-Rule MF_00102

Region

169 – 170

Substrate binding HAMAP-Rule MF_00102

Sites

Active site

159

Proton donor/acceptor Ref.8 Ref.11

Active site

163

Proton donor Ref.8 Ref.11

Binding site

NAD

Binding site

NADP

Binding site

160

Substrate

Experimental info

Mutagenesis

159

H → A or Q: 135 to 200-fold reduction in catalytic activity. Ref.11

Mutagenesis

163

K → A, C or Q: 625 to 830-fold reduction in catalytic activity. Ref.11

Secondary structure

273

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P04036 [UniParc].

Last modified November 1, 1986. Version 1.
Checksum: 0ADE6837A6CF932C
Show »

FASTA

273

28,757

        10         20         30         40         50         60 
MHDANIRVAI AGAGGRMGRQ LIQAALALEG VQLGAALERE GSSLLGSDAG ELAGAGKTGV 

        70         80         90        100        110        120 
TVQSSLDAVK DDFDVFIDFT RPEGTLNHLA FCRQHGKGMV IGTTGFDEAG KQAIRDAAAD 

       130        140        150        160        170        180 
IAIVFAANFS VGVNVMLKLL EKAAKVMGDY TDIEIIEAHH RHKVDAPSGT ALAMGEAIAH 

       190        200        210        220        230        240 
ALDKDLKDCA VYSREGHTGE RVPGTIGFAT VRAGDIVGEH TAMFADIGER LEITHKASSR 

       250        260        270 
MTFANGAVRS ALWLSGKESG LFDMRDVLDL NNL

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence and expression of the Escherichia coli dapB gene." Bouvier J., Richaud C., Richaud F., Patte J.-C., Stragier P. J. Biol. Chem. 259:14829-14834(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Systematic sequencing of the Escherichia coli genome: analysis of the 0-2.4 min region." Yura T., Mori H., Nagai H., Nagata T., Ishihama A., Fujita N., Isono K., Mizobuchi K., Nakata A. Nucleic Acids Res. 20:3305-3308(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12.
[3]	"The complete genome sequence of Escherichia coli K-12." Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y. Science 277:1453-1474(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[4]	"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T. Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[5]	"Multiple regulatory signals in the control region of the Escherichia coli carAB operon." Bouvier J., Patte J.-C., Stragier P. Proc. Natl. Acad. Sci. U.S.A. 81:4139-4143(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 269-273.
[6]	"Expression, purification, and characterization of Escherichia coli dihydrodipicolinate reductase." Reddy S.G., Sacchettini J.C., Blanchard J.S. Biochemistry 34:3492-3501(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-18, FUNCTION, KINETIC PARAMETERS, SUBSTRATE SPECIFICITY, SUBUNIT, MASS SPECTROMETRY. Strain: K12.
[7]	"Lysine represses transcription of the Escherichia coli dapB gene by preventing its activation by the ArgP activator." Bouvier J., Stragier P., Morales V., Remy E., Gutierrez C. J. Bacteriol. 190:5224-5229(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION. Strain: K12 / MG1655 / ATCC 47076.
[8]	"NMR studies uncover alternate substrates for dihydrodipicolinate synthase and suggest that dihydrodipicolinate reductase is also a dehydratase." Devenish S.R., Blunt J.W., Gerrard J.A. J. Med. Chem. 53:4808-4812(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, IDENTIFICATION OF HTPA AS REACTION SUBSTRTATE, ACTIVE SITE.
[9]	"Three-dimensional structure of Escherichia coli dihydrodipicolinate reductase." Scapin G., Blanchard J.S., Sacchettini J.C. Biochemistry 34:3502-3512(1995) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH NADPH. Strain: K12.
[10]	"Interaction of pyridine nucleotide substrates with Escherichia coli dihydrodipicolinate reductase: thermodynamic and structural analysis of binary complexes." Reddy S.G., Scapin G., Blanchard J.S. Biochemistry 35:13294-13302(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH NAD OR NUCLEOTIDE SUBSTRATE ANALOGS. Strain: K12.
[11]	"Three-dimensional structure of Escherichia coli dihydrodipicolinate reductase in complex with NADH and the inhibitor 2,6-pyridinedicarboxylate." Scapin G., Reddy S.G., Zheng R., Blanchard J.S. Biochemistry 36:15081-15088(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH NAD AND A SUBSTRATE ANALOG INHIBITOR, ENZYME REGULATION, KINETIC PARAMETERS, REACTION MECHANISM, ACTIVE SITE, SITE, MUTAGENESIS OF HIS-159 AND LYS-163. Strain: K12.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M10611 Genomic DNA. Translation: AAA23666.1.
U00096 Genomic DNA. Translation: AAC73142.1.
AP009048 Genomic DNA. Translation: BAB96600.1.
J01597 Genomic DNA. No translation available.

PIR

RDECPD. A00375.

RefSeq

NP_414572.1. NC_000913.2.
YP_488337.1. NC_007779.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ARZ	X-ray	2.60	A/B/C/D	1-273	[»]
1DIH	X-ray	2.20	A	1-273	[»]
1DRU	X-ray	2.20	A	1-273	[»]
1DRV	X-ray	2.20	A	1-273	[»]
1DRW	X-ray	2.20	A	1-273	[»]

ProteinModelPortal

P04036.

SMR

P04036. Positions 2-273.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-9399N.

IntAct

P04036. 1 interaction.

STRING

511145.b0031.

2D gel databases

SWISS-2DPAGE

P04036.

Proteomic databases

PaxDb

P04036.

PRIDE

P04036.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAC73142; AAC73142; b0031.
BAB96600; BAB96600; BAB96600.

GeneID

12932496.
944762.

KEGG

ecj:Y75_p0031.
eco:b0031.

PATRIC

32115153. VBIEscCol129921_0028.

Organism-specific databases

EchoBASE

EB0202.

EcoGene

EG10206. dapB.

Phylogenomic databases

eggNOG

COG0289.

HOGENOM

HOG000227153.

K00215.

OMA

IVMAPNM.

ProtClustDB

PRK00048.

Enzyme and pathway databases

BioCyc

EcoCyc:DIHYDROPICRED-MONOMER.
ECOL316407:JW0029-MONOMER.
MetaCyc:DIHYDROPICRED-MONOMER.

UniPathway

UPA00034; UER00018.

Gene expression databases

Genevestigator

P04036.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.

HAMAP

MF_00102. DapB.

InterPro

IPR022663. DapB_C.
IPR000846. DapB_N.
IPR022664. DapB_N_CS.
IPR011770. Dihydrodipicolinate_Rdtase.
IPR023940. Dihydrodipicolinate_Rdtase_bac.
IPR016040. NAD(P)-bd_dom.
[Graphical view]

PANTHER

PTHR20836. PTHR20836. 1 hit.

Pfam

PF05173. DapB_C. 1 hit.
PF01113. DapB_N. 1 hit.
[Graphical view]

PIRSF

PIRSF000161. DHPR. 1 hit.

TIGRFAMs

TIGR00036. dapB. 1 hit.

PROSITE

PS01298. DAPB. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P04036.

EvolutionaryTrace

P04036.

Entry information

Entry name

DAPB_ECOLI

Accession

Primary (citable) accession number: P04036

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1986
Last sequence update:	November 1, 1986
Last modified:	May 1, 2013
This is version 131 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program

Relevant documents

Escherichia coli

Escherichia coli (strain K12): entries and cross-references to EcoGene

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

2D gel databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents