EzCatDB: D00282
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DB codeD00282
RLCP classification4.1034.769660.650 : Addition
8.113.594730.651 : Isomerization
CATH domainDomain 13.30.390.10 : Enolase-like; domain 1
Domain 23.20.20.120 : TIM BarrelCatalytic domain
E.C.5.5.1.1
CSA1muc
MACiEM0269

CATH domainRelated DB codes (homologues)
3.20.20.120 : TIM BarrelD00261,D00273,D00283
3.30.390.10 : Enolase-like; domain 1D00261,D00273,D00283

Enzyme Name
UniProtKBKEGG

P08310Q51958
Protein nameMuconate cycloisomerase 1
muconate cycloisomerase
muconate cycloisomerase I
cis,cis-muconate-lactonizing enzyme
cis,cis-muconate cycloisomerase
muconate lactonizing enzyme
4-carboxymethyl-4-hydroxyisocrotonolactone lyase (decyclizing)
SynonymsEC 5.5.1.1
Cis,cis-muconate lactonizing enzyme I
MLE
Muconate cycloisomerase I
Muconate lactonizing enzyme
PfamPF02746 (MR_MLE_N)
[Graphical view]
PF02746 (MR_MLE_N)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00362Benzoate degradation via hydroxylation
MAP00364Fluorobenzoate degradation
MAP00622Toluene and xylene degradation
MAP006271,4-Dichlorobenzene degradation

UniProtKB:Accession NumberP08310Q51958
Entry nameCATB_PSEPUQ51958_PSEPU
Activity2,5-dihydro-5-oxofuran-2-acetate = cis,cis- hexadienedioate.
SubunitHomooctamer.
Subcellular location

CofactorManganese.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProductsintermediates
KEGG-idC00034C02480C04105I00069
CompoundManganesecis,cis-Muconate2,5-Dihydro-5-oxofuran-2-acetate2,5-Dihydro-5-oxofuran-2-enolate
Typeheavy metalcarboxyl groupcarboxyl group,aromatic ring (with hetero atoms other than nitrogen atoms)
ChEBI18291
35154
16508
18080

PubChem23930
5280518
542

            
1bkhA01UnboundUnboundUnbound 
1bkhB01UnboundUnboundUnbound 
1bkhC01UnboundUnboundUnbound 
1f9cA01UnboundUnboundUnbound 
1f9cB01UnboundUnboundUnbound 
1mucA01UnboundUnboundUnbound 
1mucB01UnboundUnboundUnbound 
2mucA01UnboundUnboundUnbound 
2mucB01UnboundUnboundUnbound 
3mucA01UnboundUnboundUnbound 
3mucB01UnboundUnboundUnbound 
1bkhA02UnboundUnboundUnbound 
1bkhB02UnboundUnboundUnbound 
1bkhC02UnboundUnboundUnbound 
1f9cA02Bound:_MNUnboundUnbound 
1f9cB02Bound:_MNUnboundUnbound 
1mucA02Bound:_MNUnboundUnbound 
1mucB02Bound:_MNUnboundUnbound 
2mucA02Bound:_MNUnboundUnbound 
2mucB02Bound:_MNUnboundUnbound 
3mucA02Bound:_MNUnboundUnbound 
3mucB02Bound:_MNUnboundUnbound 

Active-site residues
resource
literature [11], [15]
pdbCatalytic residuesCofactor-binding residuescomment
           
1bkhA01                       
 
 
1bkhB01                       
 
 
1bkhC01                       
 
 
1f9cA01                       
 
 
1f9cB01                       
 
 
1mucA01                       
 
 
1mucB01                       
 
 
2mucA01                       
 
 
2mucB01                       
 
 
3mucA01                       
 
mutant I54V
3mucB01                       
 
mutant I54V
1bkhA02LYS 167;LYS 169;GLU 327
ASP 198;GLU 224;ASP 249(Manganese binding)
 
1bkhB02LYS 167;LYS 169;GLU 327
ASP 198;GLU 224;ASP 249(Manganese binding)
 
1bkhC02LYS 167;LYS 169;GLU 327
ASP 198;GLU 224;ASP 249(Manganese binding)
 
1f9cA02LYS 167;LYS 169;GLU 327
ASP 198;GLU 224;ASP 249(Manganese binding)
mutant D178N
1f9cB02LYS 167;LYS 169;GLU 327
ASP 198;GLU 224;ASP 249(Manganese binding)
mutant D178N
1mucA02LYS 167;LYS 169;GLU 327
ASP 198;GLU 224;ASP 249(Manganese binding)
 
1mucB02LYS 167;LYS 169;GLU 327
ASP 198;GLU 224;ASP 249(Manganese binding)
 
2mucA02LYS 167;LYS 169;GLU 327
ASP 198;GLU 224;ASP 249(Manganese binding)
mutant F329I
2mucB02LYS 167;LYS 169;GLU 327
ASP 198;GLU 224;ASP 249(Manganese binding)
mutant F329I
3mucA02LYS 167;LYS 169;GLU 327
ASP 198;GLU 224;ASP 249(Manganese binding)
 
3mucB02LYS 167;LYS 169;GLU 327
ASP 198;GLU 224;ASP 249(Manganese binding)
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[3]p.151-152
[6]Fig.3, p.693-694
[10]Fig.3
[11]Scheme 1, p.937
[12]Fig.1, p.1159
[14]FIG.1, p.10400-10401
[15]Fig.1, p.132-135
[18]Fig.7
[21]


references
[1]
PubMed ID6652062
JournalBiochemistry
Year1983
Volume22
Pages5223-30
AuthorsNgai KL, Ornston LN, Kallen RG
TitleEnzymes of the beta-ketoadipate pathway in Pseudomonas putida: kinetic and magnetic resonance studies of the cis,cis-muconate cycloisomerase catalyzed reaction.
[2]
PubMed ID3999146
JournalJ Mol Biol
Year1985
Volume182
Pages353-5
AuthorsGoldman A, Ollis D, Ngai KL, Steitz TA
TitleCrystal structure of muconate lactonizing enzyme at 6.5 A resolution.
[3]
CommentsX-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
Medline ID87283908
PubMed ID3612800
JournalJ Mol Biol
Year1987
Volume194
Pages143-53
AuthorsGoldman A, Ollis DL, Steitz TA
TitleCrystal structure of muconate lactonizing enzyme at 3 A resolution.
Related UniProtKBP08310
[4]
PubMed ID2099737
JournalBiochem Soc Symp
Year1990
Volume57
Pages135-41
AuthorsNeidhart DC, Howell PL, Petsko GA, Gerlt JA, Kozarich JW, Powers VM, Kenyon GL
TitleRestructuring catalysis in the mandelate pathway.
[5]
PubMed ID2394680
JournalJ Bacteriol
Year1990
Volume172
Pages5119-29
AuthorsSchlomann M, Fischer P, Schmidt E, Knackmuss HJ
TitleEnzymatic formation, stability, and spontaneous reactions of 4-fluoromuconolactone, a metabolite of the bacterial degradation of 4-fluorobenzoate.
[6]
CommentsSIMILARITY TO MR.
Medline ID91015392
PubMed ID2215699
JournalNature
Year1990
Volume347
Pages692-4
AuthorsNeidhart DJ, Kenyon GL, Gerlt JA, Petsko GA
TitleMandelate racemase and muconate lactonizing enzyme are mechanistically distinct and structurally homologous.
Related UniProtKBP08310
[7]
PubMed ID1708883
JournalProteins
Year1990
Volume8
Pages334-40
AuthorsRice PA, Goldman A, Steitz TA
TitleA helix-turn-strand structural motif common in alpha-beta proteins.
[8]
PubMed ID8110801
JournalBiochemistry
Year1994
Volume33
Pages1961-70
AuthorsMazur P, Pieken WA, Budihas SR, Williams SE, Wong S, Kozarich JW
TitleCis,cis-muconate lactonizing enzyme from Trichosporon cutaneum: evidence for a novel class of cycloisomerases in eucaryotes.
[9]
PubMed ID8021223
JournalJ Bacteriol
Year1994
Volume176
Pages4366-75
AuthorsVollmer MD, Fischer P, Knackmuss HJ, Schlomann M
TitleInability of muconate cycloisomerases to cause dehalogenation during conversion of 2-chloro-cis,cis-muconate.
[10]
PubMed ID7493952
JournalJ Biol Chem
Year1995
Volume270
Pages29229-35
AuthorsBlasco R, Wittich RM, Mallavarapu M, Timmis KN, Pieper DH
TitleFrom xenobiotic to antibiotic, formation of protoanemonin from 4-chlorocatechol by enzymes of the 3-oxoadipate pathway.
[11]
CommentsX-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS).
Medline ID96107379
PubMed ID7500361
JournalJ Mol Biol
Year1995
Volume254
Pages918-41
AuthorsHelin S, Kahn PC, Guha BL, Mallows DG, Goldman A
TitleThe refined X-ray structure of muconate lactonizing enzyme from Pseudomonas putida PRS2000 at 1.85 A resolution.
Related PDB1muc
Related UniProtKBP08310
[12]
PubMed ID7855594
JournalScience
Year1995
Volume267
Pages1159-61
AuthorsBabbitt PC, Mrachko GT, Hasson MS, Huisman GW, Kolter R, Ringe D, Petsko GA, Kenyon GL, Gerlt JA
TitleA functionally diverse enzyme superfamily that abstracts the alpha protons of carboxylic acids.
[13]
PubMed ID8987982
JournalBiochemistry
Year1996
Volume35
Pages16489-501
AuthorsBabbitt PC, Hasson MS, Wedekind JE, Palmer DR, Barrett WC, Reed GH, Rayment I, Ringe D, Kenyon GL, Gerlt JA
TitleThe enolase superfamily: a general strategy for enzyme-catalyzed abstraction of the alpha-protons of carboxylic acids.
[14]
CommentsX-ray crystallography
PubMed ID9724714
JournalProc Natl Acad Sci U S A
Year1998
Volume95
Pages10396-401
AuthorsHasson MS, Schlichting I, Moulai J, Taylor K, Barrett W, Kenyon GL, Babbitt PC, Gerlt JA, Petsko GA, Ringe D
TitleEvolution of an enzyme active site: the structure of a new crystal form of muconate lactonizing enzyme compared with mandelate racemase and enolase.
Related PDB1bkh
[15]
CommentsX-ray crystallography
PubMed ID10336378
JournalProteins
Year1999
Volume34
Pages125-36
AuthorsSchell U, Helin S, Kajander T, Schlomann M, Goldman A
TitleStructural basis for the activity of two muconate cycloisomerase variants toward substituted muconates.
Related PDB2muc,3muc
[16]
PubMed ID11092867
JournalJ Bacteriol
Year2000
Volume182
Pages7044-52
AuthorsCosper NJ, Collier LS, Clark TJ, Scott RA, Neidle EL
TitleMutations in catB, the gene encoding muconate cycloisomerase, activate transcription of the distal ben genes and contribute to a complex regulatory circuit in Acinetobacter sp. strain ADP1.
[17]
CommentsX-ray crystallography
PubMed ID11080642
JournalStructure Fold Des
Year2000
Volume8
Pages1203-14
AuthorsKajander T, Kahn PC, Passila SH, Cohen DC, Lehtio L, Adolfsen W, Warwicker J, Schell U, Goldman A
TitleBuried charged surface in proteins.
Related PDB1f9c
[18]
PubMed ID11443090
JournalJ Bacteriol
Year2001
Volume183
Pages4551-61
AuthorsKaulmann U, Kaschabek SR, Schlomann M
TitleMechanism of chloride elimination from 3-chloro- and 2,4-dichloro-cis,cis-muconate: new insight obtained from analysis of muconate cycloisomerase variant CatB-K169A.
[19]
PubMed ID12218027
JournalJ Bacteriol
Year2002
Volume184
Pages5402-9
AuthorsSkiba A, Hecht V, Pieper DH
TitleFormation of protoanemonin from 2-chloro-cis,cis-muconate by the combined action of muconate cycloisomerase and muconolactone isomerase.
[20]
PubMed ID12855164
JournalFEMS Microbiol Lett
Year2003
Volume224
Pages29-34
AuthorsCha CJ, Bruce NC
TitleStereo- and regiospecific cis,cis-muconate cycloisomerization by Rhodococcus rhodochrous N75.
[21]
PubMed ID12930985
JournalProtein Sci
Year2003
Volume12
Pages1855-64
AuthorsKajander T, Lehtio L, Schlomann M, Goldman A
TitleThe structure of Pseudomonas P51 Cl-muconate lactonizing enzyme: co-evolution of structure and dynamics with the dehalogenation function.
[22]
PubMed ID15697231
JournalBiochemistry
Year2005
Volume44
Pages2059-71
AuthorsKalyanaraman C, Bernacki K, Jacobson MP
TitleVirtual screening against highly charged active sites: identifying substrates of alpha-beta barrel enzymes.

comments
This enzyme is homologous to chloromuconate cycloisomerase (E.C. 5.5.1.7; D00283 in EzCatDB), sharing the same reactions, although the homologous enzyme further catalyzes dehalogenation.
According to the literature [11], [14] and [15], this enzyme catalyzes an addition of the C1 carboxylate oxygen in substrate, muconate, to the C4 double-bonded carbon, and an isomerization, through an enolate intermediate as follows:
(A) Addition of carboxylate oxygen to the C4 double-bonded carbon, forming an enolate intermediate:
(A1) The C1 carboxylate oxygen makes a nucleophilic attack on the C4 (sp2) carbon, whereas Glu327 acts as a general acid to protonate the C6 carboxylate. The reactions lead to the formation of an enolate intermediate.
(A2) The negative charge on the enolate intermediate is stabilized by Lys167 and the Mn2+ cofactor, which is bound to Asp198, Glu224 and Asp249.
(B) Isomerization; Shift of double-bond position (from C=C-O to C-C=O):
(B1) The negative charge on the enolate oxygen is stabilized by Lys167 and the Mn2+ cofactor, which is bound to Asp198, Glu224 and Asp249.
(B2) Lys169 acts as a general acid to protonate the C5 carbon, whereas Glu327 acts as a general base to deprotonate the C6 enolate oxygen.
According to the literature in S00852 of EzCatDB, the muconate lactonizing enzymes (MLEs) convert cis,cis-muconates into muconolactones, as a part of the beta-ketoadipate pathway. This pathway consists of two branches, catechol (MLEs; E.C. 5.5.1.1) and protocatechuate (3-carboxy-cis,cis-MLEs or CMLEs; E.C. 5.5.1.2). Moreover, MLEs can be classified into three evolutionarily distinct classes. Firstly, bacterial MLEs catalyze a syn addition, using a Mn2+ cofactor with a TIM barrel fold as the catalitic domain (this entry in EzCatDB). Secondly, bacterial CMLEs (PDB;1q5n) catalyze an anti addition, without metal cofactor on a fold, which is related to class II fumarase (T00086) family (CATH 1.20.200.10). Thirdly, both eukaryotic MLEs and CMLEs catalyze a syn addition, without metal cofactor.

createdupdated
2005-05-202010-08-10


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