PDBsum entry: 1gl3

Oxidoreductase

PDB-id

1gl3

	Biological unit = asymmetric unit, as shown (as defined in PDB file)


	Main view

Contents

Description

Header details

Protein chains

Ligands

CYS

NDP ×2

Waters ×171

* Residue conservation analysis

Tools

Image Generation

AstexViewer™@PDBe

Run PROCHECK

Clefts Calculation


Right view		Bottom view

PDB id:

1gl3

Name:

Oxidoreductase

Title:

Aspartate beta-semialdehyde dehydrogenase in complex with NADP and substrate analogue s-methyl cysteine sulfoxide

Structure:

Aspartate-semialdehyde dehydrogenase. Chain: a, b. Synonym: asa dehydrogenase, asadh. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Cell_line: jm109. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_cell_line: jm109.

Biological unit:

Dimer (from PDB file)

UniProt:

Chains A, B: P0A9Q9 (DHAS_ECOLI)

Seq:

Struc:

Seq:

367 a.a.

Struc:

367 a.a.

Key:		PfamA domain
		Secondary structure			CATH domain

Enzyme class:

E.C.1.2.1.11 [IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

L-aspartate 4-semialdehyde + phosphate + NADP⁺ = L-4-aspartyl phosphate + NADPH (see diagram below)

Pathway:

Lysine biosynthesis (early stages)

Resolution:

2.60Å

R-factor:

0.200

R-free:

0.262

Authors:

A.T.Hadfield,G.Kryger,J.Ouyang,D.Ringe,G.A.Petsko,R.E.Viola

Key ref:

A.Hadfield et al. (2001). Active site analysis of the potential antimicrobial target aspartate semialdehyde dehydrogenase.. Biochemistry, 40, 14475-14483. [PubMed id: 11724560] [DOI: 10.1021/bi015713o]

Date:

23-Aug-01

Release date:

01-Nov-01

Related entries:

1brm aspartate beta-semialdehyde dehydrogenase from escherichia coli

Quick_links

RCSB

PDBe

SRS

MMDB

JenaLib

OCA

PDBWiki

Proteopedia

CATH

SCOP

FSSP

HSSP

PDBSWS

PQS

CSA

ProSAT

Whatcheck

EDS

Procheck

Clefts

Surface

Enzyme reaction for E.C.1.2.1.11

L-aspartate-4-semialdehyde

phosphate

NADP(+)
Bound ligand (Het Group name = NDP)
corresponds exactly

L-4-aspartyl phosphate

NADPH

Molecule diagrams generated from .mol files obtained from the KEGG ftp site.

Key reference

DOI no: 10.1021/bi015713o Biochemistry 40:14475-14483 (2001)

PubMed id: 11724560

Active site analysis of the potential antimicrobial target aspartate semialdehyde dehydrogenase.

A.Hadfield, C.Shammas, G.Kryger, D.Ringe, G.A.Petsko, J.Ouyang, R.E.Viola.

ABSTRACT

Aspartate-beta-semialdehyde dehydrogenase (ASADH) lies at the first branch point in the biosynthetic pathway through which bacteria, fungi, and the higher plants synthesize amino acids, including lysine and methionine and the cell wall component diaminopimelate from aspartate. Blocks in this biosynthetic pathway, which is absent in mammals, are lethal, and inhibitors of ASADH may therefore serve as useful antibacterial, fungicidal, or herbicidal agents. We have determined the structure of ASADH from Escherichia coli by crystallography in the presence of its coenzyme and a substrate analogue that acts as a covalent inhibitor. This structure is comparable to that of the covalent intermediate that forms during the reaction catalyzed by ASADH. The key catalytic residues are confirmed as cysteine 135, which is covalently linked to the intermediate during the reaction, and histidine 274, which acts as an acid/base catalyst. The substrate and coenzyme binding residues are also identified, and these active site residues are conserved throughout all of the ASADH sequences. Comparison of the previously determined apo-enzyme structure [Hadfield et al. J. Mol. Biol. and the complex presented here reveals a conformational change that occurs on binding of NADP that creates a binding site for the amino acid substrate. These results provide a structural explanation for the preferred order of substrate binding that is observed kinetically.

Literature references that cite this PDB file's key reference

PubMed id Reference

20124701 B.T.Arachea, X.Liu, A.G.Pavlovsky, and R.E.Viola (2010).
Expansion of the aspartate beta-semialdehyde dehydrogenase family: the first structure of a fungal ortholog.

Acta Crystallogr D Biol Crystallogr, 66, 205-212.

18236087 A.Singh, H.R.Kushwaha, and P.Sharma (2008).
Molecular modelling and comparative structural account of aspartyl beta-semialdehyde dehydrogenase of Mycobacterium tuberculosis (H37Rv).

J Mol Model, 14, 249-263.

16895909 C.R.Faehnle, J.Le Coq, X.Liu, and R.E.Viola (2006).
Examination of key intermediates in the catalytic cycle of aspartate-beta-semialdehyde dehydrogenase from a gram-positive infectious bacteria.

J Biol Chem, 281, 31031-31040.

PDB codes: 2gyy 2gz1 2gz2 2gz3

16525757 R.A.Azevedo, M.Lancien, and P.J.Lea (2006).
The aspartic acid metabolic pathway, an exciting and essential pathway in plants.

Amino Acids, 30, 143-162.

16261551 R.J.Cox, J.S.Gibson, and A.T.Hadfield (2005).
Design, synthesis and analysis of inhibitors of bacterial aspartate semialdehyde dehydrogenase.

Chembiochem, 6, 2255-2260.

16240442 T.Nonaka, A.Kita, J.Miura-Ohnuma, E.Katoh, N.Inagaki, T.Yamazaki, and K.Miki (2005).
Crystal structure of putative N-acetyl-gamma-glutamyl-phosphate reductase (AK071544) from rice (Oryza sativa).

Proteins, 61, 1137-1140.

PDB code: 2cvo

15583380 C.R.Faehnle, J.Blanco, and R.E.Viola (2004).
Structural basis for discrimination between oxyanion substrates or inhibitors in aspartate-beta-semialdehyde dehydrogenase.

Acta Crystallogr D Biol Crystallogr, 60, 2320-2324.

PDB codes: 1ta4 1tb4

15272161 J.Blanco, R.A.Moore, C.R.Faehnle, D.M.Coe, and R.E.Viola (2004).
The role of substrate-binding groups in the mechanism of aspartate-beta-semialdehyde dehydrogenase.

Acta Crystallogr D Biol Crystallogr, 60, 1388-1395.

PDB codes: 1oza 1pqp 1pqu 1pr3 1ps8 1pu2 1q2x

15388927 J.Blanco, R.A.Moore, C.R.Faehnle, and R.E.Viola (2004).
Critical catalytic functional groups in the mechanism of aspartate-beta-semialdehyde dehydrogenase.

Acta Crystallogr D Biol Crystallogr, 60, 1808-1815.

14559965 J.Blanco, R.A.Moore, and R.E.Viola (2003).
Capture of an intermediate in the catalytic cycle of L-aspartate-beta-semialdehyde dehydrogenase.

Proc Natl Acad Sci U S A, 100, 12613-12617.

PDB codes: 1nwc 1nwh 1nx6

12493825 J.Blanco, R.A.Moore, V.Kabaleeswaran, and R.E.Viola (2003).
A structural basis for the mechanism of aspartate-beta-semialdehyde dehydrogenase from Vibrio cholerae.

Protein Sci, 12, 27-33.

PDB codes: 1mb4 1mc4

12496312 Z.Yang, A.Savchenko, A.Yakunin, R.Zhang, A.Edwards, C.Arrowsmith, and L.Tong (2003).
Aspartate dehydrogenase, a novel enzyme identified from structural and functional studies of TM1643.

J Biol Chem, 278, 8804-8808.

PDB code: 1h2h

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.