DB code: T00407

RLCP classification 6.30.97700.5320 : Double-bonded atom exchange
8.1121121.660330.5528 : Isomerization
5.524.3198500.5541 : Elimination
6.40.521000.5530 : Double-bonded atom exchange
CATH domain 2.10.25.30 : Laminin Catalytic domain
3.40.640.10 : Aspartate Aminotransferase; domain 2 Catalytic domain
3.90.1150.10 : Aspartate Aminotransferase, domain 1
E.C. 4.4.1.4
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
Q01594 Alliin lyase 1
Alliinase-1
EC 4.4.1.4
Cysteine sulphoxide lyase 1
PF04864 (Alliinase_C)
PF04863 (EGF_alliinase)
[Graphical View]

KEGG enzyme name
Alliin lyase
Alliinase
Cysteine sulfoxide lyase
Alkylcysteine sulfoxide lyase
S-alkylcysteine sulfoxide lyase
L-cysteine sulfoxide lyase
S-alkyl-L-cysteine sulfoxide lyase
Alliin alkyl-sulfenate-lyase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q01594 ALLN1_ALLSA An S-alkyl-L-cysteine S-oxide = an alkyl sulfenate + 2-aminoacrylate. Homodimer. Vacuole. Pyridoxal phosphate.

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00018 C00698 C03726 C02245 C02218 I00185 I00071 I00184 I00171
E.C.
Compound Pyridoxal phosphate Cl- S-alkyl-L-cysteine S-oxide alkyl sulfenate 2-aminoacrylate Geminal-diamine transition-state (active-site Lys-PLP-S-alkyl-L-cysteine S-oxide) External aldimine intermediate (PLP-S-alkyl-L-cysteine S-oxide) Quinonoid intermediate (PLP-S-alkyl-cysteine S-oxide) Aminoacrylate intermediate (PLP-dehydroAla)
Type aromatic ring (with nitrogen atoms),phosphate group/phosphate ion halide amino acids,sulfoxide group sulfenic acid amino acids
ChEBI 18405
17996
17123
76565
PubChem 1051
312
123991
72551549
1lk9A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:_CL Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1lk9B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:_CL Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2horA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:_CL Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2hoxA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:_CL Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2hoxB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:_CL Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2hoxC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:_CL Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2hoxD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:_CL Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1lk9A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1lk9B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:PLP Unbound Unbound Unbound Unbound Transition-state-analogue:PLP-DHA-LYS_251 Unbound Unbound Unbound
2horA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2hoxA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:P1T Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-bound:P1T
2hoxB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:P1T Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-bound:P1T
2hoxC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:P1T Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-bound:P1T
2hoxD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:P1T Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-bound:P1T
1lk9A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1lk9B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2horA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2hoxA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2hoxB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2hoxC03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2hoxD03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Literature [3], [4]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1lk9A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 63;TYR 92 PHE 94;SER 98;PHE 100 (Chloride binding) GLY 64
1lk9B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 63;TYR 92 PHE 94;SER 98;PHE 100 (Chloride binding) GLY 64
2horA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 63;TYR 92 PHE 94;SER 98;PHE 100 (Chloride binding) GLY 64
2hoxA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 63;TYR 92 PHE 94;SER 98;PHE 100 (Chloride binding) GLY 64
2hoxB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 63;TYR 92 PHE 94;SER 98;PHE 100 (Chloride binding) GLY 64
2hoxC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 63;TYR 92 PHE 94;SER 98;PHE 100 (Chloride binding) GLY 64
2hoxD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 63;TYR 92 PHE 94;SER 98;PHE 100 (Chloride binding) GLY 64
1lk9A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 165;ASP 225;TYR 228;LYS 251 LYS 251 (PLP binding)
1lk9B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 165;ASP 225;TYR 228;LYS 251 LYS 251 (PLP binding)
2horA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 165;ASP 225;TYR 228;LYS 251 LYS 251 (PLP binding)
2hoxA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 165;ASP 225;TYR 228;LYS 251 LYS 251 (PLP binding)
2hoxB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 165;ASP 225;TYR 228;LYS 251 LYS 251 (PLP binding)
2hoxC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 165;ASP 225;TYR 228;LYS 251 LYS 251 (PLP binding)
2hoxD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 165;ASP 225;TYR 228;LYS 251 LYS 251 (PLP binding)
1lk9A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1lk9B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2horA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2hoxA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2hoxB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2hoxC03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2hoxD03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
Scheme 1
[4]
Scheme 1

References
[1]
Resource
Comments
Medline ID
PubMed ID 9799098
Journal Eur J Biochem
Year 1998
Volume 257
Pages 21-30
Authors Manabe T, Hasumi A, Sugiyama M, Yamazaki M, Saito K
Title Alliinase [S-alk(en)yl-L-cysteine sulfoxide lyase] from Allium tuberosum (Chinese chive)--purification, localization, cDNA cloning and heterologous functional expression.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 9914259
Journal Curr Opin Struct Biol
Year 1998
Volume 8
Pages 759-69
Authors Jansonius JN
Title Structure, evolution and action of vitamin B6-dependent enzymes.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.53 ANGSTROMS) OF 39-465, SUBUNIT.
Medline ID
PubMed ID 12235163
Journal J Biol Chem
Year 2002
Volume 277
Pages 46402-7
Authors Kuettner EB, Hilgenfeld R, Weiss MS
Title The active principle of garlic at atomic resolution.
Related PDB 1lk9
Related UniProtKB Q01594
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 39-465, SUBUNIT.
Medline ID
PubMed ID 17174334
Journal J Mol Biol
Year 2007
Volume 366
Pages 611-25
Authors Shimon LJ, Rabinkov A, Shin I, Miron T, Mirelman D, Wilchek M, Frolow F
Title Two structures of alliinase from Alliium sativum L.: apo form and ternary complex with aminoacrylate reaction intermediate covalently bound to the PLP cofactor.
Related PDB 2hor 2hox
Related UniProtKB Q01594

Comments
This enzyme belongs to the class-I of PLP-dependent enzymes superfamily (see [3]).
This enzyme cleaves the beta-carbon-gamma-sulfur bond of sulfoxide derivatives of cysteine to produce allicin, with its C-S lyase activity (see [3], [4]).
This enzyme catalyzes the following reactions (see [2], [3], [4]):
(A) Formation of external aldimine (with amine group of S-alkyl-L-cysteine sulfoxide); Exchange of double-bonded atoms (or transaldimination)
(B) Isomerization (shift of double-bond position) forming a quinonoid intermediate (I00184)
(C) Eliminative double-bond formation (C-S lysis from the intermediate) leading to formation of an aminoacrylate-PLP intermediate (I00171) and a product, alkyl sulfenate
(D) Formation of internal aldimine of PLP with active-site Lys, releasing another product, 2-aminoacrylate; Exchange of double-bonded atoms (or transaldimination)
These reactions proceed in the following way (see [3], [4], and D00101, D00085):
(A) Formation of external aldimine (with amine group of S-alkyl-L-cysteine sulfoxide); Exchange of double-bonded atoms (or transaldimination)
(A1) Tyr228 interacts with O3' atom of PLP, modulating and keeping the O3' of PLP negatively charged. The negatively charged O3 atom of PLP modulates the pKa of the amine group of substrate, S-alkyl-L-cysteine sulfoxie, and also the pKa of the internal aldimine with Lys251. The difference in the pKa values facilitates the proton transfer from the amine group of the substrate to the epsilon-nitrogen of Lys251.
(A2) The amine group of the substrate makes a nucleophilic attak on the C4' of the internal aldimine, and Lys251 is released from the Schiff-base (or the internal aldimine), forming a geminal-diamine transition-state (I00185).
(A3) Proton transfer from the substrate-derived amine group to epsilon-nitrogen atom of Lys251 must occur.
(A4) The lone pair of the amine group of the substrate makes a nucleophilic attack on the C4' atom to form a double-bond, releasing the amine of Lys251, leading to the formation of the external aldimine (I00071).
(B) Isomerization (shift of double-bond position) forming a quinonoid intermediate (I00184)
(B0) Asp225 interacts with the N1 atom of PLP, modulating and enhancing the activity of the PLP cofactor as an electron sink, which facilitates the abstraction of alpha-proton from the substrate covalently bound to the PLP (I00071). At the same time, Tyr228 also interacts with the O3' atom of the PLP, modulating the activity of the PLP, whereas Tyr165 stabilizes the PLP through ring stacking interactions.
(B1) The protonated sidechain of Lys251 must be activated. Either Tyr228 or Tyr92' from adjacent subunit may activate Lys251.
(B2) The activated Lys251 acts as a general base to deprotonate alpha-carbon of the external aldimine intermediate (I00071), forming a quinonoid intermediate (I00184).
(C) Eliminative double-bond formation (C-S lysis from the intermediate) leading to formation of an aminoacrylate-PLP intermediate (I00171) and a product, alkyl sulfenate
(C0) Asp225 interacts with the N1 atom of PLP, modulating and enhancing the activity of the PLP cofactor, which facilitates the following elimination reaction. At the same time, Tyr228 also interacts with the O3' atom of the PLP, modulating the activity of the PLP, whereas Tyr165 stabilizes the PLP through ring stacking interactions. Meanwhile, sidechain of Ser63 and mainchain amide of Gly64 may stabilize the eliminated sulfoxide group.
(C1) The protonated Lys251 may act as a general acid to protonate the eliminated sulfoxide group, releasing alkyl sulfenate and leading to the elimination and formation of an aminoacrylate-PLP intermediate (I00171).
(D) Formation of internal aldimine of PLP with active-site Lys, releasing another product, 2-aminoacrylate; Exchange of double-bonded atoms (or transaldimination)
## This reaction is the reverse reaction of reaction (A).
(D1) Tyr228 interacts with O3' atom of PLP, modulating and keeping the O3' of PLP negatively charged.
(D2) The amine group of the Lys251 makes a nucleophilic attak on the C4' of the external aldimine, and the aminoacrylate is released from the Schiff-base (or the external aldimine), forming a geminal-diamine transition-state.
(D3) Proton transfer from the epsilon-nitrogen atom of Lys251 to the amine group of the leaving group must occur.
(D4) The lone pair of the amine group of Lys251 makes a nucleophilic attack on the C4' atom to form a double-bond, releasing the amine group of aminoacrylate, leading to the formation of the internal aldimine.

Created Updated
2010-08-05 2015-07-29