PDBsum entry 1jsc

Lyase

PDB id

1jsc

Loading ...

Contents

			Protein chains

					541 a.a. *

			Ligands

					2HP ×3


					TPP ×2


					FAD ×2

			Metals

					__K ×2


					_MG ×2

			Waters ×325

* Residue conservation analysis

PDB id:

1jsc

Links

Name:

Lyase

Title:

Crystal structure of the catalytic subunit of yeast acetohydroxyacid synthase: a target for herbicidal inhibitors

Structure:

Acetohydroxy-acid synthase. Chain: a, b. Fragment: mature catalytic subunit. Synonym: acetolactate synthase. Engineered: yes

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Gene: ilv2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PQS)

Resolution:

2.60Å

R-factor:

0.188

R-free:

0.219

Authors:

S.S.Pang,R.G.Duggleby,L.W.Guddat

Key ref:

S.S.Pang et al. (2002). Crystal structure of yeast acetohydroxyacid synthase: a target for herbicidal inhibitors. J Mol Biol, 317, 249-262. PubMed id: 11902841 DOI: 10.1006/jmbi.2001.5419

Date:

17-Aug-01

Release date:

16-Jan-02

PROCHECK

	Headers

	References

Protein chains

P07342 (ILVB_YEAST) - Acetolactate synthase catalytic subunit, mitochondrial from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: Struc:

Seq: Struc:					687 a.a. 541 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.2.2.1.6 - acetolactate synthase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Pathway:

Isoleucine and Valine Biosynthesis

Reaction:

2 pyruvate + H⁺ = (2S)-2-acetolactate + CO2

2 × pyruvate	+	H(+)	=	(2S)-2-acetolactate	+	CO2

Cofactor:

Thiamine diphosphate

Thiamine diphosphate
Bound ligand (Het Group name = TPP) corresponds exactly

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

reference

DOI no: 10.1006/jmbi.2001.5419	J Mol Biol 317:249-262 (2002)
PubMed id: 11902841

Crystal structure of yeast acetohydroxyacid synthase: a target for herbicidal inhibitors.
S.S.Pang, R.G.Duggleby, L.W.Guddat.

ABSTRACT

Acetohydroxyacid synthase (AHAS; EC 4.1.3.18) catalyzes the first step in branched-chain amino acid biosynthesis. The enzyme requires thiamin diphosphate and FAD for activity, but the latter is unexpected, because the reaction involves no oxidation or reduction. Due to its presence in plants, AHAS is a target for sulfonylurea and imidazolinone herbicides. Here, the crystal structure to 2.6 A resolution of the catalytic subunit of yeast AHAS is reported. The active site is located at the dimer interface and is near the proposed herbicide-binding site. The conformation of FAD and its position in the active site are defined. The structure of AHAS provides a starting point for the rational design of new herbicides.

Selected figure(s)



	Figure 7. Figure 7. (a) A schematic diagram illustrating the residues contacting the ThDP molecule. (b) View of the active site showing the relative locations of ThDP, Mg2+ and the flavin ring of FAD in the dimer interface of yeast AHAS. (c) Contacts between AHAS, ThDP and Mg2+. Coordination distances shown as broken lines to Mg2+ are in the range 2.0-2.3 Å.		Figure 9. Figure 9. Proposed interaction of AHAS and the herbicidal inhibitor, imazapyr, which was docked into the enzyme using the program GOLD. [37] Amino acid residues at herbicide-resistance sites are labeled and shown as CPK models.

Figures were selected by the author.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20107768

M.Kyselková, J.Janata, M.Ságová-Marecková, and J.Kopecký (2010).
Subunit-subunit interactions are weakened in mutant forms of acetohydroxy acid synthase insensitive to valine inhibition.

Arch Microbiol, 192, 195-200.

20383786

N.M.Karanth, and S.P.Sarma (2010).
1H, 13C, 15N assignments of the dimeric regulatory subunit (ilvN) of the E. coli AHAS I.

Biomol NMR Assign, 4, 131-133.

20192743

S.B.Powles, and Q.Yu (2010).
Evolution in action: plants resistant to herbicides.

Annu Rev Plant Biol, 61, 317-347.

19476487

K.Tittmann (2009).
Reaction mechanisms of thiamin diphosphate enzymes: redox reactions.

FEBS J, 276, 2454-2468.

18478622

F.Q.Ji, C.W.Niu, C.N.Chen, Q.Chen, G.F.Yang, Z.Xi, and C.G.Zhan (2008).
Computational design and discovery of conformationally flexible inhibitors of acetohydroxyacid synthase to overcome drug resistance associated with the W586L mutation.

ChemMedChem, 3, 1203-1206.

18080290

G.H.Liu, Y.N.Xue, X.Q.Lu, M.M.Liu, W.Y.Wang, and L.Z.Yang (2008).
Pyrimidinyl-substituted amides and thioureas: syntheses, crystal structure and herbicidal activities.

Pest Manag Sci, 64, 556-564.

19381469

J.Kopecký, M.Kyselková, L.Sigutová, S.Pospísil, J.Felsberg, J.Spízek, and J.Janata (2008).
Deregulation of acetohydroxy-acid synthase: Loss of allosteric inhibition conferred by mutations in the catalytic subunit.

Folia Microbiol (Praha), 53, 467-471.

18988747

P.Neumann, A.Weidner, A.Pech, M.T.Stubbs, and K.Tittmann (2008).
Structural basis for membrane binding and catalytic activation of the peripheral membrane enzyme pyruvate oxidase from Escherichia coli.

Proc Natl Acad Sci U S A, 105, 17390-17395.

PDB codes:

3ey9 3eya

18422645

S.Ronconi, R.Jonczyk, and U.Genschel (2008).
A novel isoform of pantothenate synthetase in the Archaea.

FEBS J, 275, 2754-2764.

18084069

C.L.Berthold, D.Gocke, M.D.Wood, F.J.Leeper, M.Pohl, and G.Schneider (2007).
Structure of the branched-chain keto acid decarboxylase (KdcA) from Lactococcus lactis provides insights into the structural basis for the chemoselective and enantioselective carboligation reaction.

Acta Crystallogr D Biol Crystallogr, 63, 1217-1224.

PDB codes:

2vbf 2vbg

18007037

E.C.Juan, M.M.Hoque, M.T.Hossain, T.Yamamoto, S.Imamura, K.Suzuki, T.Sekiguchi, and A.Takénaka (2007).
The structures of pyruvate oxidase from Aerococcus viridans with cofactors and with a reaction intermediate reveal the flexibility of the active-site tunnel for catalysis.

Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 900-907.

PDB codes:

1v5f 1v5g 2dji

17391016

H.Xie, S.Vucetic, L.M.Iakoucheva, C.J.Oldfield, A.K.Dunker, Z.Obradovic, and V.N.Uversky (2007).
Functional anthology of intrinsic disorder. 3. Ligands, post-translational modifications, and diseases associated with intrinsically disordered proteins.

J Proteome Res, 6, 1917-1932.

17612488

S.Watanabe, R.Matsumi, T.Arai, H.Atomi, T.Imanaka, and K.Miki (2007).
Crystal structures of [NiFe] hydrogenase maturation proteins HypC, HypD, and HypE: insights into cyanation reaction by thiol redox signaling.

Mol Cell, 27, 29-40.

PDB codes:

2z1c 2z1d 2z1e 2z1f

17660691

T.Ohsako, and T.Tominaga (2007).
Nucleotide substitutions in the acetolactate synthase genes of sulfonylurea-resistant biotypes of Monochoria vaginalis (Pontederiaceae).

Genes Genet Syst, 82, 207-215.

16699828

J.A.McCourt, and R.G.Duggleby (2006).
Acetohydroxyacid synthase and its role in the biosynthetic pathway for branched-chain amino acids.

Amino Acids, 31, 173-210.

16407096

J.A.McCourt, S.S.Pang, J.King-Scott, L.W.Guddat, and R.G.Duggleby (2006).
Herbicide-binding sites revealed in the structure of plant acetohydroxyacid synthase.

Proc Natl Acad Sci U S A, 103, 569-573.

PDB codes:

1ybh 1yhy 1yhz 1yi0 1yi1 1z8n

16868987

Z.Xi, Z.Yu, C.Niu, S.Ban, and G.Yang (2006).
Development of a general quantum-chemical descriptor for steric effects: density functional theory based QSAR study of herbicidal sulfonylurea analogues.

J Comput Chem, 27, 1571-1576.

16216870

C.L.Berthold, P.Moussatche, N.G.Richards, and Y.Lindqvist (2005).
Structural basis for activation of the thiamin diphosphate-dependent enzyme oxalyl-CoA decarboxylase by adenosine diphosphate.

J Biol Chem, 280, 41645-41654.

PDB code:

2c31

16055369

D.M.Chipman, R.G.Duggleby, and K.Tittmann (2005).
Mechanisms of acetohydroxyacid synthases.

Curr Opin Chem Biol, 9, 475-481.

16511076

E.A.Sieminska, A.Macova, D.R.Palmer, and D.A.Sanders (2005).
Crystallization and preliminary X-ray analysis of (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate (SHCHC) synthase (MenD) from Escherichia coli.

Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 489-492.

16374672

J.G.Wang, Z.M.Li, N.Ma, B.L.Wang, L.Jiang, S.S.Pang, Y.T.Lee, L.W.Guddat, and R.G.Duggleby (2005).
Structure-activity relationships for a new family of sulfonylurea herbicides.

J Comput Aided Mol Des, 19, 801-820.

15752351

R.Golbik, L.E.Meshalkina, T.Sandalova, K.Tittmann, E.Fiedler, H.Neef, S.König, R.Kluger, G.A.Kochetov, G.Schneider, and G.Hübner (2005).
Effect of coenzyme modification on the structural and catalytic properties of wild-type transketolase and of the variant E418A from Saccharomyces cerevisiae.

FEBS J, 272, 1326-1342.

15627242

S.Tan, R.R.Evans, M.L.Dahmer, B.K.Singh, and D.L.Shaner (2005).
Imidazolinone-tolerant crops: history, current status and future.

Pest Manag Sci, 61, 246-257.

16302970

T.G.Mosbacher, M.Mueller, and G.E.Schulz (2005).
Structure and mechanism of the ThDP-dependent benzaldehyde lyase from Pseudomonas fluorescens.

FEBS J, 272, 6067-6076.

PDB codes:

2ag0 2ag1

14623876

M.E.Caines, J.M.Elkins, K.S.Hewitson, and C.J.Schofield (2004).
Crystal structure and mechanistic implications of N2-(2-carboxyethyl)arginine synthase, the first enzyme in the clavulanic acid biosynthesis pathway.

J Biol Chem, 279, 5685-5692.

PDB codes:

1upa 1upb 1upc

15044456

S.Engel, M.Vyazmensky, M.Vinogradov, D.Berkovich, A.Bar-Ilan, U.Qimron, Y.Rosiansky, Z.Barak, and D.M.Chipman (2004).
Role of a conserved arginine in the mechanism of acetohydroxyacid synthase: catalysis of condensation with a specific ketoacid substrate.

J Biol Chem, 279, 24803-24812.

14557277

S.S.Pang, R.G.Duggleby, R.L.Schowen, and L.W.Guddat (2004).
The crystal structures of Klebsiella pneumoniae acetolactate synthase with enzyme-bound cofactor and with an unusual intermediate.

J Biol Chem, 279, 2242-2253.

PDB codes:

1n0h 1ozf 1ozg 1ozh

12651851

E.M.Ciszak, L.G.Korotchkina, P.M.Dominiak, S.Sidhu, and M.S.Patel (2003).
Structural basis for flip-flop action of thiamin pyrophosphate-dependent enzymes revealed by human pyruvate dehydrogenase.

J Biol Chem, 278, 21240-21246.

PDB code:

1ni4

12904299

G.Zhang, J.Dai, Z.Lu, and D.Dunaway-Mariano (2003).
The phosphonopyruvate decarboxylase from Bacteroides fragilis.

J Biol Chem, 278, 41302-41308.

14621995

M.Bhasin, J.L.Billinsky, and D.R.Palmer (2003).
Steady-state kinetics and molecular evolution of Escherichia coli MenD [(1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase], an anomalous thiamin diphosphate-dependent decarboxylase-carboligase.

Biochemistry, 42, 13496-13504.

12471039

N.U.Gamage, R.G.Duggleby, A.C.Barnett, M.Tresillian, C.F.Latham, N.E.Liyou, M.E.McManus, and J.L.Martin (2003).
Structure of a human carcinogen-converting enzyme, SULT1A1. Structural and kinetic implications of substrate inhibition.

J Biol Chem, 278, 7655-7662.

PDB code:

1ls6

12823560

R.G.Duggleby, S.S.Pang, H.Yu, and L.W.Guddat (2003).
Systematic characterization of mutations in yeast acetohydroxyacid synthase. Interpretation of herbicide-resistance data.

Eur J Biochem, 270, 2895-2904.

12496246

S.S.Pang, L.W.Guddat, and R.G.Duggleby (2003).
Molecular basis of sulfonylurea herbicide inhibition of acetohydroxyacid synthase.

J Biol Chem, 278, 7639-7644.

PDB code:

1n0h

12077455

S.S.Pang, L.W.Guddat, and R.G.Duggleby (2002).
Crystallization of the FAD-independent acetolactate synthase of Klebsiella pneumoniae.

Acta Crystallogr D Biol Crystallogr, 58, 1237-1239.

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.