P44801 (DHAS_HAEIN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Aspartate-semialdehyde dehydrogenase
Short name=ASA dehydrogenase
Short name=ASADH
EC=1.2.1.11

Alternative name(s):
Aspartate-beta-semialdehyde dehydrogenase

Gene names

Name:	asd
Ordered Locus Names:	HI_0646

Organism

Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) [Reference proteome] [HAMAP]

Taxonomic identifier

71421 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Proteobacteria › Gammaproteobacteria › Pasteurellales › Pasteurellaceae › Haemophilus › Haemophilus influenzae

Protein attributes

Sequence length	371 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the NADPH-dependent formation of L-aspartate-semialdehyde (L-ASA) by the reductive dephosphorylation of L-aspartyl-4-phosphate. Ref.2
Catalytic activity	L-aspartate 4-semialdehyde + phosphate + NADP+ = L-4-aspartyl phosphate + NADPH. Ref.2 Ref.4
Pathway	Amino-acid biosynthesis; L-lysine biosynthesis via DAP pathway; (S)-tetrahydrodipicolinate from L-aspartate: step 2/4. HAMAP-Rule MF_02121 Amino-acid biosynthesis; L-methionine biosynthesis via de novo pathway; L-homoserine from L-aspartate: step 2/3. HAMAP-Rule MF_02121 Amino-acid biosynthesis; L-threonine biosynthesis; L-threonine from L-aspartate: step 2/5. HAMAP-Rule MF_02121
Subunit structure	Homodimer. Ref.3
Domain	Consists of two domains, an N-terminal nucleotide-binding domain and a C-terminal dimerization domain. Ref.3
Sequence similarities	Belongs to the aspartate-semialdehyde dehydrogenase family.
Biophysicochemical properties	Kinetic parameters: KM=0.24 mM for L-aspartate 4-semialdehyde Ref.2 Ref.4 KM=0.15 mM for NADP+ KM=1.6 mM for phosphate

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Diaminopimelate biosynthesis Lysine biosynthesis Methionine biosynthesis Threonine biosynthesis
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	'de novo' L-methionine biosynthetic process Inferred from electronic annotation. Source: HAMAP diaminopimelate biosynthetic process Inferred from electronic annotation. Source: HAMAP isoleucine biosynthetic process Inferred from electronic annotation. Source: InterPro lysine biosynthetic process via diaminopimelate Inferred from electronic annotation. Source: HAMAP threonine biosynthetic process Inferred from electronic annotation. Source: HAMAP
Cellular_component	cytoplasm Inferred from electronic annotation. Source: InterPro
Molecular_function	N-acetyl-gamma-glutamyl-phosphate reductase activity Inferred from electronic annotation. Source: InterPro NAD binding Inferred from electronic annotation. Source: InterPro NADP binding Inferred from electronic annotation. Source: HAMAP aspartate-semialdehyde dehydrogenase activity 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 – 371

371

Aspartate-semialdehyde dehydrogenase HAMAP-Rule MF_02121

PRO_0000141375

Regions

Nucleotide binding

10 – 13

4

NADP HAMAP-Rule MF_02121

Nucleotide binding

37 – 38

2

NADP HAMAP-Rule MF_02121

Sites

Active site

136

1

Acyl-thioester intermediate

Active site

277

1

Proton acceptor

Binding site

74

1

NADP

Binding site

103

1

Phosphate

Binding site

163

1

Substrate

Binding site

166

1

NADP; via carbonyl oxygen

Binding site

243

1

Substrate

Binding site

246

1

Phosphate

Binding site

270

1

Substrate

Binding site

353

1

NADP

Experimental info

Mutagenesis

103

1

R → K: 2-fold increase in affinity for ASA, 23-fold decrease in affinity for phosphate, and 275-fold decrease in activity. Ref.4

Mutagenesis

103

1

R → L: 7-fold increase in affinity for ASA, 150-fold decrease in affinity for phosphate, and 1400-fold decrease in activity. Ref.4

Mutagenesis

243

1

E → D: No change in affinity for ASA and 82-fold decrease in activity. Ref.4

Mutagenesis

246

1

K → R: 2-fold increase in affinity for ASA, nearly no change in affinity for phosphate, and 30-fold decrease in activity. Ref.4

Mutagenesis

270

1

R → K: 2-fold decrease in affinity for ASA and 825-fold decrease in activity. Ref.4

Secondary structure

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371

Helix Strand Turn

Details...

Beta strand

2 – 8

7

Helix

12 – 24

13

Turn

25 – 29

5

Beta strand

30 – 38

9

Helix

47 – 49

3

Helix

61 – 64

4

Beta strand

68 – 72

5

Helix

76 – 88

13

Beta strand

93 – 100

8

Turn

101 – 104

4

Beta strand

108 – 111

4

Helix

113 – 126

14

Beta strand

130 – 133

4

Helix

136 – 150

15

Beta strand

154 – 163

10

Helix

165 – 167

3

Helix

170 – 185

16

Helix

188 – 191

4

Helix

198 – 209

12

Turn

217 – 219

3

Beta strand

225 – 228

4

Turn

236 – 238

3

Helix

242 – 255

14

Beta strand

258 – 260

3

Beta strand

264 – 267

4

Beta strand

270 – 287

18

Helix

291 – 300

10

Beta strand

303 – 307

5

Helix

312 – 318

7

Helix

321 – 324

4

Beta strand

330 – 338

9

Beta strand

341 – 352

12

Turn

353 – 358

6

Helix

359 – 370

12

Sequences

	Sequence		Length	Mass (Da)
	P44801 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: E44CE5B90F2AF041	FASTA	371	40,539
	10 20 30 40 50 60 MKNVGFIGWR GMVGSVLMDR MSQENDFENL NPVFFTTSQA GQKAPVFGGK DAGDLKSAFD 70 80 90 100 110 120 IEELKKLDII VTCQGGDYTN EVYPKLKATG WDGYWVDAAS ALRMKDDAII VLDPVNQHVI 130 140 150 160 170 180 SEGLKKGIKT FVGGNCTVSL MLMAIGGLFE KDLVEWISVA TYQAASGAGA KNMRELLSQM 190 200 210 220 230 240 GLLEQAVSSE LKDPASSILD IERKVTAKMR ADNFPTDNFG AALGGSLIPW IDKLLPETGQ 250 260 270 280 290 300 TKEEWKGYAE TNKILGLSDN PIPVDGLCVR IGALRCHSQA FTIKLKKDLP LEEIEQIIAS 310 320 330 340 350 360 HNEWVKVIPN DKEITLRELT PAKVTGTLSV PVGRLRKLAM GPEYLAAFTV GDQLLWGAAE 370 PVRRILKQLV A

References

	« Hide 'large scale' referencesShow '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. , 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]	"Expression and purification of aspartate beta-semialdehyde dehydrogenase from infectious microorganisms." Moore R.A., Bocik W.E., Viola R.E. Protein Expr. Purif. 25:189-194(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, KINETIC PARAMETERS. Strain: ATCC 51907 / DSM 11121 / KW20 / Rd.
[3]	"Capture of an intermediate in the catalytic cycle of L-aspartate-beta-semialdehyde dehydrogenase." Blanco J., Moore R.A., Viola R.E. Proc. Natl. Acad. Sci. U.S.A. 100:12613-12617(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF APOENZYME AND IN COMPLEX WITH L-ASPARTATE-SEMIALDEHYDE AND PHOSPHATE, SUBUNIT, DOMAIN, CATALYTIC MECHANISM. Strain: ATCC 51907 / DSM 11121 / KW20 / Rd.
[4]	"The role of substrate-binding groups in the mechanism of aspartate-beta-semialdehyde dehydrogenase." Blanco J., Moore R.A., Faehnle C.R., Coe D.M., Viola R.E. Acta Crystallogr. D 60:1388-1395(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF MUTANTS LEU-103; LYS-103; SER-136; ASP-243; ARG-246; LYS-270 AND ASN-277 IN COMPLEX WITH NADP, CATALYTIC ACTIVITY, KINETIC STUDIES, MUTAGENESIS OF ARG-103; GLU-243; LYS-246 AND ARG-270. Strain: ATCC 51907 / DSM 11121 / KW20 / Rd.
[5]	"Structural basis for discrimination between oxyanion substrates or inhibitors in aspartate-beta-semialdehyde dehydrogenase." Faehnle C.R., Blanco J., Viola R.E. Acta Crystallogr. D 60:2320-2324(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEXES WITH ARSENATE AND PERIODATE IONS. Strain: ATCC 51907 / DSM 11121 / KW20 / Rd.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L42023 Genomic DNA. Translation: AAC22306.1.

PIR

B64084.

RefSeq

NP_438806.1. NC_000907.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NWC	X-ray	2.04	A/B	1-371	[»]
1NWH	X-ray	2.00	A/B	1-371	[»]
1NX6	X-ray	2.15	A	1-371	[»]
1OZA	X-ray	2.06	A	1-371	[»]
1PQP	X-ray	2.06	A	1-371	[»]
1PQU	X-ray	1.92	A/B/C/D	1-371	[»]
1PR3	X-ray	2.15	A	1-371	[»]
1PS8	X-ray	2.40	A	1-371	[»]
1PU2	X-ray	2.06	A	1-371	[»]
1Q2X	X-ray	2.05	A/B	1-371	[»]
1TA4	X-ray	2.28	A	1-371	[»]
1TB4	X-ray	2.15	A	1-371	[»]

ProteinModelPortal

P44801.

SMR

P44801. Positions 1-371.

ModBase

Search...

Protein-protein interaction databases

STRING

71421.HI0646.

Proteomic databases

PRIDE

P44801.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAC22306; AAC22306; HI_0646.

GeneID

949960.

KEGG

hin:HI0646.

PATRIC

20189907. VBIHaeInf48452_0675.

Phylogenomic databases

eggNOG

COG0136.

KO

K00133.

OMA

SCQGGDY.

ProtClustDB

PRK06598.

Enzyme and pathway databases

BRENDA

1.2.1.11. 2529.

UniPathway

UPA00034; UER00016.
UPA00050; UER00463.
UPA00051; UER00464.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.

HAMAP

MF_02121. ASADH.

InterPro

IPR000319. Asp-semialdehyde_DH_CS.
IPR011534. Asp_ADH_gamma-type.
IPR012080. Asp_semialdehyde_DH.
IPR016040. NAD(P)-bd_dom.
IPR000534. Semialdehyde_DH_NAD-bd.
IPR012280. Semialdhyde_DH_dimer_dom.
[Graphical view]

Pfam

PF01118. Semialdhyde_dh. 1 hit.
PF02774. Semialdhyde_dhC. 1 hit.
[Graphical view]

PIRSF

PIRSF000148. ASA_dh. 1 hit.

SMART

SM00859. Semialdhyde_dh. 1 hit.
[Graphical view]

TIGRFAMs

TIGR01745. asd_gamma. 1 hit.

PROSITE

PS01103. ASD. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P44801.

Entry information

Entry name

DHAS_HAEIN

Accession

Primary (citable) accession number: P44801

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 105 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program