DB code: S00023

CATH domain	1.10.590.10 : Chorismate Mutase, subunit A	Catalytic domain
E.C.	5.4.99.5
CSA	3csm
M-CSA	3csm
MACiE	M0081

CATH domain	Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB	Protein name	Synonyms	RefSeq	Pfam
P32178	Chorismate mutase	CM EC 5.4.99.5	NP_015385.1 (Protein) NM_001184157.1 (DNA/RNA sequence)	PF01817 (CM_2) [Graphical View]

KEGG enzyme name
chorismate mutase hydroxyphenylpyruvate synthase

UniprotKB: Accession Number	Entry name	Activity	Subunit	Subcellular location	Cofactor
P32178	CHMU_YEAST	Chorismate = prephenate.	Homodimer.

KEGG Pathways
Map code	Pathways	E.C.
MAP00400	Phenylalanine, tyrosine and tryptophan biosynthesis

Compound table
	Substrates	Products	Intermediates
KEGG-id	C00251	C00254
E.C.
Compound	Chorismate	Prephenate
Type	carbohydrate,carboxyl group	carbohydrate,carboxyl group
ChEBI	17333 17333	84387 84387
PubChem	12039 12039

1csmA	Unbound	Unbound	Unbound
1csmB	Unbound	Unbound	Unbound
2csmA	Unbound	Unbound	Unbound
3csmA	Unbound	Unbound	Transition-state-analogue:TSA
3csmB	Unbound	Unbound	Transition-state-analogue:TSA
4csmA	Unbound	Unbound	Transition-state-analogue:TSA
4csmB	Unbound	Unbound	Transition-state-analogue:TSA
5csmA	Unbound	Unbound	Unbound

Reference for Active-site residues
resource	references	E.C.
literature [7], [9], [14]

Active-site residues
PDB	Catalytic residues	Cofactor-binding residues	Modified residues	Main-chain involved in catalysis	Comment

1csmA	LYS 168;GLU 246				mutant T226I
1csmB	LYS 168;GLU 246				mutant T226I
2csmA	LYS 168;GLU 246
3csmA	LYS 168;GLU 246
3csmB	LYS 168;GLU 246
4csmA	LYS 168;GLU 246
4csmB	LYS 168;GLU 246
5csmA	LYS 168;GLU 246				mutant T226S

References for Catalytic Mechanism
References	Sections	No. of steps in catalysis
[5]	Fig.1, p.10597-10598
[6]	p.3332-3333
[7]	Fig.1, p.1446
[9]	Fig.2, p.14644-14645
[14]	Fig.2, p.410-411
[15]	Fig.1

References
[1]
Resource
Comments
Medline ID
PubMed ID	2187528
Journal	Biochemistry
Year	1990
Volume	29
Pages	3660-8
Authors	Schmidheini T, Mosch HU, Evans JN, Braus G
Title	Yeast allosteric chorismate mutase is locked in the activated state by a single amino acid substitution.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID	8218394
Journal	Biochim Biophys Acta
Year	1993
Volume	1203
Pages	71-6
Authors	Ramilo C, Braus G, Evans JN
Title	A tyrosine residue is involved in the allosteric binding of tryptophan to yeast chorismate mutase.
Related PDB
Related UniProtKB
[3]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
Medline ID	95062155
PubMed ID	7971967
Journal	Proc Natl Acad Sci U S A
Year	1994
Volume	91
Pages	10814-8
Authors	Xue Y, Lipscomb WN, Graf R, Schnappauf G, Braus G
Title	The crystal structure of allosteric chorismate mutase at 2.2-A resolution.
Related PDB	1csm
Related UniProtKB	P32178
[4]
Resource
Comments
Medline ID
PubMed ID	7883726
Journal	J Bacteriol
Year	1995
Volume	177
Pages	1645-8
Authors	Graf R, Dubaquie Y, Braus GH
Title	Modulation of the allosteric equilibrium of yeast chorismate mutase by variation of a single amino acid residue.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID	7479847
Journal	Proc Natl Acad Sci U S A
Year	1995
Volume	92
Pages	10595-8
Authors	Xue Y, Lipscomb WN
Title	Location of the active site of allosteric chorismate mutase from Saccharomyces cerevisiae, and comments on the catalytic and regulatory mechanisms.
Related PDB
Related UniProtKB
[6]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
Medline ID	96194968
PubMed ID	8622937
Journal	Proc Natl Acad Sci U S A
Year	1996
Volume	93
Pages	3330-4
Authors	Strater N, Hakansson K, Schnappauf G, Braus G, Lipscomb WN
Title	Crystal structure of the T state of allosteric yeast chorismate mutase and comparison with the R state.
Related PDB	2csm
Related UniProtKB	P32178
[7]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID	98046093
PubMed ID	9384560
Journal	Structure
Year	1997
Volume	5
Pages	1437-52
Authors	Strater N, Schnappauf G, Braus G, Lipscomb WN
Title	Mechanisms of catalysis and allosteric regulation of yeast chorismate mutase from crystal structures.
Related PDB	3csm 4csm 5csm
Related UniProtKB	P32178
[8]
Resource
Comments
Medline ID
PubMed ID	9299331
Journal	J Mol Biol
Year	1997
Volume	271
Pages	838-45
Authors	Lin SL, Xu D, Li A, Rosen M, Wolfson HJ, Nussinov R
Title	Investigation of the enzymatic mechanism of the yeast chorismate mutase by docking a transition state analog.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID	9843942
Journal	Proc Natl Acad Sci U S A
Year	1998
Volume	95
Pages	14640-5
Authors	Ma J, Zheng X, Schnappauf G, Braus G, Karplus M, Lipscomb WN
Title	Yeast chorismate mutase in the R state: simulations of the active site.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID	9501182
Journal	Proc Natl Acad Sci U S A
Year	1998
Volume	95
Pages	2868-73
Authors	Schnappauf G, Lipscomb WN, Braus GH
Title	Separation of inhibition and activation of the allosteric yeast chorismate mutase.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID	9626703
Journal	Proteins
Year	1998
Volume	31
Pages	445-52
Authors	Lin SL, Xu D, Li A, Nussinov R
Title	Electrostatics, allostery, and activity of the yeast chorismate mutase.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID	9843375
Journal	Biochemistry
Year	1998
Volume	37
Pages	15703-12
Authors	Christendat D, Saridakis VC, Turnbull JL
Title	Use of site-directed mutagenesis to identify residues specific for each reaction catalyzed by chorismate mutase-prephenate dehydrogenase from Escherichia coli.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID	10894726
Journal	J Bacteriol
Year	2000
Volume	182
Pages	4188-97
Authors	Krappmann S, Pries R, Gellissen G, Hiller M, Braus GH
Title	HARO7 encodes chorismate mutase of the methylotrophic yeast Hansenula polymorpha and is derepressed upon methanol utilization.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID	11528003
Journal	Microbiol Mol Biol Rev
Year	2001
Volume	65
Pages	404-21, table of contents
Authors	Helmstaedt K, Krappmann S, Braus GH
Title	Allosteric regulation of catalytic activity: Escherichia coli aspartate transcarbamoylase versus yeast chorismate mutase.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID	11481470
Journal	Proc Natl Acad Sci U S A
Year	2001
Volume	98
Pages	9032-7
Authors	Guo H, Cui Q, Lipscomb WN, Karplus M
Title	Substrate conformational transitions in the active site of chorismate mutase: their role in the catalytic mechanism.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID	11997452
Journal	Proc Natl Acad Sci U S A
Year	2002
Volume	99
Pages	6631-6
Authors	Helmstaedt K, Heinrich G, Lipscomb WN, Braus GH
Title	Refined molecular hinge between allosteric and catalytic domain determines allosteric regulation and stability of fungal chorismate mutase.
Related PDB
Related UniProtKB

Comments
This enzyme has an allosteric site, to which tryptophan (for activation) or tyrosine (for inhibition) is bound. The site is separate from the active site. According to the literature [9] & [14], this enzyme catalyzes Claisen rearrangement or concerted addition and elimination. According to the literature [7], [9] & [14], Glu246 can be mutated to glutamine residue, as it is a glutamine residue in the counterparts of E. coli and bacteria. Although the wild-type enzyme has an optimum in acidic pH, E246Q mutant has catalytic activity over a broad pH range (see [14]).

Comments

This enzyme has an allosteric site, to which tryptophan (for activation) or tyrosine (for inhibition) is bound. The site is separate from the active site.
According to the literature [9] & [14], this enzyme catalyzes Claisen rearrangement or concerted addition and elimination.
According to the literature [7], [9] & [14], Glu246 can be mutated to glutamine residue, as it is a glutamine residue in the counterparts of E. coli and bacteria. Although the wild-type enzyme has an optimum in acidic pH, E246Q mutant has catalytic activity over a broad pH range (see [14]).

Created	Updated
2005-06-17	2009-02-26