KEGG   ENZYME: 4.1.1.90Help
Entry
EC 4.1.1.90                 Enzyme                                 
Name
peptidyl-glutamate 4-carboxylase;
vitamin K-dependent carboxylase;
gamma-glutamyl carboxylase
Class
Lyases;
Carbon-carbon lyases;
Carboxy-lyases
BRITE hierarchy
Sysname
peptidyl-glutamate 4-carboxylase (2-methyl-3-phytyl-1,4-naphthoquinone-epoxidizing)
Reaction(IUBMB)
peptidyl-4-carboxyglutamate + 2,3-epoxyphylloquinone + H2O = peptidyl-glutamate + CO2 + O2 + phylloquinone [RN:R05144]
Reaction(KEGG)
R05144;
(other) R09991
Show
Substrate
peptidyl-4-carboxyglutamate [CPD:C06246];
2,3-epoxyphylloquinone [CPD:C05849];
H2O [CPD:C00001]
Product
peptidyl-glutamate [CPD:C06247];
CO2 [CPD:C00011];
O2 [CPD:C00007];
phylloquinone [CPD:C02059]
Comment
The enzyme can use various vitamin-K derivatives, including menaquinone, but does not contain iron. In the reverse direction the mechanism appears to involve the generation of a strong base by oxygenation of vitamin K. It catalyses the post-translational modification of several proteins of the blood-clotting system. 9--12 glutamate residues are converted to 4-carboxyglutamate (Gla) in a specific domain of the target protein. The 4-pro-S hydrogen of the glutamate residue is removed [5] and there is an inversion of stereochemistry at this position [6].
Pathway
Ubiquinone and other terpenoid-quinone biosynthesis
Orthology
K10106  
vitamin K-dependent gamma-carboxylase
Genes
HSA: 
2677(GGCX)
PTR: 
459364(GGCX)
PPS: 
100979139(GGCX)
GGO: 
101133597(GGCX)
PON: 
100171564(GGCX)
MCC: 
695628(GGCX)
MMU: 
56316(Ggcx)
RNO: 
81716(Ggcx)
CFA: 
475769(GGCX)
AML: 
FCA: 
101085622(GGCX)
BTA: 
281190(GGCX)
SSC: 
100620337
ECB: 
100067312
MDO: 
100030057
OAA: 
100077833
TGU: 
100221126
ACS: 
100555036
XLA: 
444473(ggcx)
XTR: 
100144666(ggcx)
DRE: 
100537604
TRU: 
101067681
OLA: 
101172424
BFO: 
BRAFLDRAFT_92865
CIN: 
100183699
SPU: 
764318
DME: 
Dmel_CG13927(GC)
DPO: 
Dpse_GA12632
DAN: 
Dana_GF24021
DER: 
Dere_GG14584
DPE: 
Dper_GL20734
DSE: 
Dsec_GM14197
DSI: 
Dsim_GD13462
DWI: 
Dwil_GK23671
DYA: 
Dyak_GE20943
DGR: 
Dgri_GH14871
DMO: 
Dmoj_GI12843
DVI: 
Dvir_GJ12988
AGA: 
AgaP_AGAP006363
AAG: 
AaeL_AAEL002622
CQU: 
CpipJ_CPIJ007343
AME: 
551869(GC)
NVI: 
100123716(NV11811)
TCA: 
659418
API: 
100161672
PHU: 
Phum_PHUM216730
ISC: 
IscW_ISCW020855
NVE: 
NEMVE_v1g187853
HMG: 
100204648
TAD: 
TRIADDRAFT_30063
 » show all
Taxonomy
Reference
1  [PMID:7569894]
  Authors
Dowd P, Hershline R, Ham SW, Naganathan S
  Title
Vitamin K and energy transduction: a base strength amplification mechanism.
  Journal
Science. 269 (1995) 1684-91.
Reference
2  [PMID:10068650]
  Authors
Furie B, Bouchard BA, Furie BC
  Title
Vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid.
  Journal
Blood. 93 (1999) 1798-808.
Reference
3  [PMID:17073445]
  Authors
Rishavy MA, Hallgren KW, Yakubenko AV, Shtofman RL, Runge KW, Berkner KL
  Title
Bronsted analysis reveals Lys218 as the carboxylase active site base that deprotonates vitamin K hydroquinone to initiate vitamin K-dependent protein carboxylation.
  Journal
Biochemistry. 45 (2006) 13239-48.
Reference
4  [PMID:17935315]
  Authors
Silva PJ, Ramos MJ
  Title
Reaction mechanism of the vitamin K-dependent glutamate carboxylase: a computational study.
  Journal
J. Phys. Chem. B. 111 (2007) 12883-7.
Reference
5  [PMID:6150930]
  Authors
Decottignies-Le Marechal P, Ducrocq C, Marquet A, Azerad R
  Title
The stereochemistry of hydrogen abstraction in vitamin K-dependent carboxylation.
  Journal
J. Biol. Chem. 259 (1984) 15010-2.
Reference
6  [PMID:1931973]
  Authors
Dubois J, Dugave C, Foures C, Kaminsky M, Tabet JC, Bory S, Gaudry M, Marquet A
  Title
Vitamin K dependent carboxylation: determination of the stereochemical course using 4-fluoroglutamyl-containing substrate.
  Journal
Biochemistry. 30 (1991) 10506-12.
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 
DBGET integrated database retrieval system