EzCatDB: S00852
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DB codeS00852
RLCP classification4.1034.143290.135 : Addition
8.113.46500.4 : Isomerization
CATH domainDomain 12.130.10.10 : Methylamine Dehydrogenase; Chain HCatalytic domain
E.C.5.5.1.5
CSA1jof

CATH domainRelated DB codes (homologues)
2.130.10.10 : Methylamine Dehydrogenase; Chain HD00039,M00329

Enzyme Name
UniProtKBKEGG

P38677
Protein nameCarboxy-cis,cis-muconate cyclaseCarboxy-cis,cis-muconate cyclase
3-Carboxymuconate cyclase
SynonymsEC 5.5.1.5
3-carboxy-cis,cis-muconate lactonizing enzyme
CMLE
RefSeqXP_957686.1 (Protein)
XM_952593.1 (DNA/RNA sequence)
PfamPF10282 (Lactonase)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00362Benzoate degradation via hydroxylation

UniProtKB:Accession NumberP38677
Entry nameCMLE_NEUCR
Activity3-Carboxy-2,5-dihydro-5-oxofuran-2-acetate = 3-carboxy-cis,cis-muconate.
SubunitHomotetramer.
Subcellular location
CofactorDoes not require divalent cations for activity.

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC01163C04553I00068
Compound3-Carboxy-cis,cis-muconate3-Carboxy-2,5-dihydro-5-oxofuran-2-acetate3-carboxy-2,5-dihydro-5-oxofuran-2-enolate
Typecarboxyl groupcarboxyl group,aromatic ring (with hetero atoms other than nitrogen atoms)
ChEBI15749
16989

PubChem5280404
440383

           
1jofA00UnboundUnboundUnbound
1jofB00UnboundUnboundUnbound
1jofC00UnboundUnboundUnbound
1jofD00UnboundUnboundUnbound
1jofE00UnboundUnboundUnbound
1jofF00UnboundUnboundUnbound
1jofG00UnboundUnboundUnbound
1jofH00UnboundUnboundUnbound

Active-site residues
resource
literature [4]
pdbCatalytic residues
         
1jofA00HIS 148;ARG 196;GLU 212;ARG 274
1jofB00HIS 148;ARG 196;GLU 212;ARG 274
1jofC00HIS 148;ARG 196;GLU 212;ARG 274
1jofD00HIS 148;ARG 196;GLU 212;ARG 274
1jofE00HIS 148;ARG 196;GLU 212;ARG 274
1jofF00HIS 148;ARG 196;GLU 212;ARG 274
1jofG00HIS 148;ARG 196;GLU 212;ARG 274
1jofH00HIS 148;ARG 196;GLU 212;ARG 274

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[4]Fig.3, p.488

references
[1]
PubMed ID8132467
JournalJ Bacteriol
Year1994
Volume176
Pages1718-28
AuthorsMazur P, Henzel WJ, Mattoo S, Kozarich JW
Title3-Carboxy-cis,cis-muconate lactonizing enzyme from Neurospora crassa: an alternate cycloisomerase motif.
[2]
PubMed ID15299752
JournalActa Crystallogr D Biol Crystallogr
Year1996
Volume52
Pages221-3
AuthorsGlumoff T, Helin S, Mazur P, Kozarich JW, Goldman A
TitleCrystallization and preliminary crystallographic analysis of 3-carboxy-cis,cis-muconate lactonizing enzyme from Neurospora crassa.
[3]
PubMed ID11976482
JournalActa Crystallogr D Biol Crystallogr
Year2002
Volume58
Pages727-34
AuthorsMerckel MC, Kajander T, Deacon AM, Thompson A, Grossmann JG, Kalkkinen N, Goldman A
Title3-Carboxy-cis,cis-muconate lactonizing enzyme from Neurospora crassa: MAD phasing with 80 selenomethionines.
[4]
PubMed ID11937053
JournalStructure
Year2002
Volume10
Pages483-92
AuthorsKajander T, Merckel MC, Thompson A, Deacon AM, Mazur P, Kozarich JW, Goldman A
TitleThe structure of Neurospora crassa 3-carboxy-cis,cis-muconate lactonizing enzyme, a beta propeller cycloisomerase.
Related PDB1jof

comments
According to the literature [3] and [4], 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) (see [3] and [4]).
Moreover, MLEs can be classified into three evolutionarily distinct classes (see [3] and [4]). Firstly, bacterial MLEs catalyze a syn addition, using a Mn2+ cofactor with a TIM barrel fold as the catalitic domain (D00282 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. This entry belongs to the CMLEs in the third class.
According to the literature [4], this enzyme catalyzes an intramolecular addition reaction 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 sidechains of Arg196 and Arg274 seem to modulate and increase the nucleophilicity of the C1 carboxylate of the substrate, 3-carboxylate-cis,cis-muconate, by interacting with it.
(A2) The C1 carboxylate oxygen makes a nucleophilic attack on the C4 (sp2) carbon, whereas Glu212 acts as a general acid to protonate the C6 carboxylate. The reactions lead to the formation of an enolate intermediate.
(B) Isomerization; Shift of double-bond position (from C=C-O to C-C=O):
(B1) His148 seems to act as a general acid to protonate the C5 carbon in the enolate intermediate. (Here, Glu212 must act as a general base to deprotonate the C6 enolate oxygen. Otherwise, it must be difficult to convert the enolate intermediate to the product.)
## Although the literature [4] described His148 as a general base, it seems to act as a general acid in the forward reaction (from the substrate to product). However, it will be a genral base in the reverse reaction.

createdupdated
2009-09-092010-08-05


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