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P44859 (DAPF_HAEIN) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Diaminopimelate epimerase

Short name=DAP epimerase
EC=5.1.1.7
Alternative name(s):
PLP-Independent Amino Acid Racemases
Gene names
Name:dapF
Ordered Locus Names:HI_0750
OrganismHaemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) [Reference proteome] [HAMAP]
Taxonomic identifier71421 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaPasteurellalesPasteurellaceaeHaemophilus

Protein attributes

Sequence length274 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the stereoinversion of LL-2,6-diaminoheptanedioate (L,L-DAP) to meso-diaminoheptanedioate (meso-DAP), a precursor of L-lysine and an essential component of the bacterial peptidoglycan. Only accepts DAP isomers with the L configuration. Ref.2

Catalytic activity

LL-2,6-diaminoheptanedioate = meso-diaminoheptanedioate. Ref.2

Enzyme regulation

Inhibited by LL-aziridino (LL-AziDAP), DL-aziridino (DL-AziDAP), (2S,3R,6S)-2,6-diamino-3-fluoropimelate (L,L-3-fluoro-DAP) and (2R,3S,6S)-2,6-diamino-3-fluoropimelate (D,L-3-fluoro-DAP). Ref.3 Ref.6

Pathway

Amino-acid biosynthesis; L-lysine biosynthesis via DAP pathway; DL-2,6-diaminopimelate from LL-2,6-diaminopimelate: step 1/1. HAMAP-Rule MF_00197

Subunit structure

Monomer. Ref.4

Subcellular location

Cytoplasm HAMAP-Rule MF_00197.

Sequence similarities

Belongs to the diaminopimelate epimerase family.

Biophysicochemical properties

Kinetic parameters:

Kcat is 128 and 82 (sec-1) for L,L-DAP and D,L-DAP, respectively.

KM=0.7 mM for L,L-DAP (at pH 7.8) Ref.2

KM=1.1 mM for D,L-DAP (at pH 7.8)

Ontologies

Keywords
   Biological processAmino-acid biosynthesis
Lysine biosynthesis
   Cellular componentCytoplasm
   Molecular functionIsomerase
   PTMDisulfide bond
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processlysine biosynthetic process via diaminopimelate

Inferred from electronic annotation. Source: UniProtKB-HAMAP

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functiondiaminopimelate epimerase activity

Inferred from electronic annotation. Source: UniProtKB-HAMAP

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 274274Diaminopimelate epimerase HAMAP-Rule MF_00197
PRO_0000149842

Regions

Region8 – 92Substrate HAMAP-Rule MF_00197
Region73 – 753Substrate binding HAMAP-Rule MF_00197
Region208 – 2092Substrate binding HAMAP-Rule MF_00197
Region218 – 2192Substrate binding HAMAP-Rule MF_00197

Sites

Active site731Proton donor/acceptor Ref.3 Ref.4
Active site2171Proton donor/acceptor Ref.3 Ref.4
Binding site111Substrate
Binding site441Substrate
Binding site641Substrate
Binding site1571Substrate
Binding site1901Substrate
Site1591Important for catalytic activity Potential
Site2081Important for catalytic activity Potential

Amino acid modifications

Disulfide bond73 ↔ 217 Ref.4

Experimental info

Mutagenesis731C → A: Inactive as epimerases, but it is able to rapidly catalyze the HF eliminatio via abstraction of the C-2 hydrogen of the D,L-3-fluoro-DAP analog and is essentially unable to catalyze the same elimination with the L,L-3-fluoro-DAP analog. Ref.3 Ref.7
Mutagenesis731C → S: It is able to catalyze both epimerization of DAP and HF elimination of L,L-3-fluoro-DAP and D,L-3-fluoro-DAP. Able to slowly eliminate HF but does not catalyze epimerization; when associated with S-217. Ref.3 Ref.7
Mutagenesis2171C → A: Inactive as epimerases. It is able to rapidly catalyze the HF eliminatio via abstraction of the C-2 hydrogen of the L,L-3-fluoro-DAP analog and is essentially unable to catalyze the same elimination with the D,L-3-fluoro-DAP analog. Ref.3 Ref.7
Mutagenesis2171C → S: It is able to catalyze both epimerization of DAP and HF elimination of L,L-3-fluoro-DAP and D,L-3-fluoro-DAP. Able to slowly eliminate HF but does not catalyze epimerization; when associated with S-73. Ref.3 Ref.7

Secondary structure

.................................................. 274
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P44859 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 321B3CDAFFE81EDA

FASTA27430,249
        10         20         30         40         50         60 
MQFSKMHGLG NDFVVVDGVT QNVFFTPETI RRLANRHCGI GFDQLLIVEA PYDPELDFHY 

        70         80         90        100        110        120 
RIFNADGSEV SQCGNGARCF ARFVTLKGLT NKKDISVSTQ KGNMVLTVKD DNQIRVNMGE 

       130        140        150        160        170        180 
PIWEPAKIPF TANKFEKNYI LRTDIQTVLC GAVSMGNPHC VVQVDDIQTA NVEQLGPLLE 

       190        200        210        220        230        240 
SHERFPERVN AGFMQIINKE HIKLRVYERG AGETQACGSG ACAAVAVGIM QGLLNNNVQV 

       250        260        270 
DLPGGSLMIE WNGVGHPLYM TGEATHIYDG FITL 

« Hide

References

« Hide 'large scale' references
[1]"Whole-genome random sequencing and assembly of Haemophilus influenzae Rd."
Fleischmann R.D., Adams M.D., White O., Clayton R.A., Kirkness E.F., Kerlavage A.R., Bult C.J., Tomb J.-F., Dougherty B.A., Merrick J.M., McKenney K., Sutton G.G., FitzHugh W., Fields C.A., Gocayne J.D., Scott J.D., Shirley R., Liu L.-I. expand/collapse author list , Glodek A., Kelley J.M., Weidman J.F., Phillips C.A., Spriggs T., Hedblom E., Cotton M.D., Utterback T.R., Hanna M.C., Nguyen D.T., Saudek D.M., Brandon R.C., Fine L.D., Fritchman J.L., Fuhrmann J.L., Geoghagen N.S.M., Gnehm C.L., McDonald L.A., Small K.V., Fraser C.M., Smith H.O., Venter J.C.
Science 269:496-512(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 51907 / DSM 11121 / KW20 / Rd.
[2]"Chemical mechanism of Haemophilus influenzae diaminopimelate epimerase."
Koo C.W., Blanchard J.S.
Biochemistry 38:4416-4422(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, REACTION MECHANISM, BIOPHYSICOCHEMICAL PROPERTIES.
[3]"Identification of active site cysteine residues that function as general bases: diaminopimelate epimerase."
Koo C.W., Sutherland A., Vederas J.C., Blanchard J.S.
J. Am. Chem. Soc. 122:6122-6123(2000)
Cited for: MUTAGENESIS OF CYS-73 AND CYS-217, ACTIVE SITE, ENZYME REGULATION.
[4]"Structural symmetry: the three-dimensional structure of Haemophilus influenzae diaminopimelate epimerase."
Cirilli M., Zheng R., Scapin G., Blanchard J.S.
Biochemistry 37:16452-16458(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.72 ANGSTROMS), ACTIVE SITE, DISULFIDE BOND, SUBUNIT.
[5]"Refinement of Haemophilus influenzae diaminopimelic acid epimerase (DapF) at 1.75 A resolution suggests a mechanism for stereocontrol during catalysis."
Lloyd A.J., Huyton T., Turkenburg J., Roper D.I.
Acta Crystallogr. D 60:397-400(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS), REACTION MECHANISM.
[6]"Structural insights into stereochemical inversion by diaminopimelate epimerase: an antibacterial drug target."
Pillai B., Cherney M.M., Diaper C.M., Sutherland A., Blanchard J.S., Vederas J.C., James M.N.
Proc. Natl. Acad. Sci. U.S.A. 103:8668-8673(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS, SUBSTRATE SPECIFICITY, ENZYME REGULATION.
[7]"Dynamics of catalysis revealed from the crystal structures of mutants of diaminopimelate epimerase."
Pillai B., Cherney M., Diaper C.M., Sutherland A., Blanchard J.S., Vederas J.C., James M.N.
Biochem. Biophys. Res. Commun. 363:547-553(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF MUTANT SER-73 AND SER-217 IN COMPLEX WITH SUBSTRATE ANALOGS, MUTAGENESIS OF CYS-73 AND CYS-217.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L42023 Genomic DNA. Translation: AAC22409.1.
PIRF64090.
RefSeqNP_438909.1. NC_000907.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1BWZX-ray2.72A1-274[»]
1GQZX-ray1.75A1-274[»]
2GKEX-ray1.35A1-274[»]
2GKJX-ray1.70A1-274[»]
2Q9HX-ray2.30A1-274[»]
2Q9JX-ray2.20A1-274[»]
ProteinModelPortalP44859.
SMRP44859. Positions 1-274.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING71421.HI0750.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAC22409; AAC22409; HI_0750.
GeneID949560.
KEGGhin:HI0750.
PATRIC20190143. VBIHaeInf48452_0787.

Phylogenomic databases

eggNOGCOG0253.
KOK01778.
OMACFARFVL.
OrthoDBEOG6ND0M5.
ProtClustDBPRK00450.

Enzyme and pathway databases

UniPathwayUPA00034; UER00025.

Family and domain databases

HAMAPMF_00197. DAP_epimerase.
InterProIPR018510. DAP_epimerase_AS.
IPR001653. DAP_epimerase_DapF.
[Graphical view]
PANTHERPTHR31689:SF0. PTHR31689:SF0. 1 hit.
PfamPF01678. DAP_epimerase. 2 hits.
[Graphical view]
TIGRFAMsTIGR00652. DapF. 1 hit.
PROSITEPS01326. DAP_EPIMERASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP44859.

Entry information

Entry nameDAPF_HAEIN
AccessionPrimary (citable) accession number: P44859
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: February 19, 2014
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

Haemophilus influenzae

Haemophilus influenzae (strain Rd): entries and gene names