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;
peptidyl-glutamate 4-carboxylase (2-methyl-3-phytyl-1,4-naphthoquinone-epoxidizing)
Class
Lyases;
Carbon-carbon lyases;
Carboxy-lyases
BRITE hierarchy
Sysname
peptidyl-glutamate 4-carboxylase (2-methyl-3-phytyl-1,4-naphthoquinol-epoxidizing)
Reaction(IUBMB)
peptidyl-4-carboxyglutamate + 2,3-epoxyphylloquinone + H2O = peptidyl-glutamate + CO2 + O2 + phylloquinol [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];
phylloquinol [CPD:C03313]
Comment
The enzyme can use various vitamin-K derivatives, including menaquinol, but does not contain iron. The mechanism appears to involve the generation of a strong base by oxygenation of vitamin K. It catalyses the post-translational carboxylation of glutamate residues 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].
History
EC 4.1.1.90 created 2009, modified 2011
Pathway
ec00130  Ubiquinone and other terpenoid-quinone biosynthesis
ec01110  Biosynthesis of secondary metabolites
Orthology
K10106  vitamin K-dependent gamma-carboxylase
Genes
HSA: 2677(GGCX)
PTR: 459364(GGCX)
PPS: 100979139(GGCX)
GGO: 101133597(GGCX)
PON: 100171564(GGCX)
NLE: 100605566(GGCX)
MCC: 695628(GGCX)
MCF: 102116153(GGCX)
CSAB: 103219944(GGCX)
RRO: 104677047(GGCX)
RBB: 108518115(GGCX)
CJC: 100412061(GGCX)
SBQ: 101035344(GGCX)
MMU: 56316(Ggcx)
RNO: 81716(Ggcx)
CGE: 100774482(Ggcx)
NGI: 103739792(Ggcx)
HGL: 101703456(Ggcx)
CCAN: 109686177(Ggcx)
OCU: 100346091(GGCX)
TUP: 102479702(GGCX)
CFA: 475769(GGCX)
AML: 100477985(GGCX)
UMR: 103671848(GGCX)
ORO: 101380661(GGCX)
FCA: 101085622(GGCX)
PTG: 102962433(GGCX)
AJU: 106978202(GGCX)
BTA: 281190(GGCX)
BOM: 102277857(GGCX)
BIU: 109566174(GGCX)
PHD: 102319966(GGCX)
CHX: 102170242(GGCX)
OAS: 443129(GGCX)
SSC: 100620337(GGCX)
CFR: 102506387(GGCX)
CDK: 105104153(GGCX)
BACU: 103007146(GGCX)
LVE: 103089680(GGCX)
OOR: 101285440(GGCX)
ECB: 100067312(GGCX)
EPZ: 103548273(GGCX)
EAI: 106838601(GGCX)
MYB: 102242720(GGCX)
MYD: 102767774(GGCX)
HAI: 109371334(GGCX)
RSS: 109436168(GGCX)
PALE: 102898204(GGCX)
LAV: 100675417(GGCX)
TMU: 101340769
MDO: 100030057(GGCX)
OAA: 100077833
MGP: 104916860(GGCX)
CJO: 107323599(GGCX)
TGU: 100221126(GGCX)
FAB: 101818545(GGCX)
PHI: 102110670(GGCX)
PMAJ: 107213872(GGCX)
CCW: 104683151(GGCX)
CLV: 102090925(GGCX)
AAM: 106493802(GGCX)
ASN: 102383382(GGCX)
AMJ: 106737680 109282852(GGCX)
PSS: 102449866(GGCX)
CMY: 102930896(GGCX)
CPIC: 101940387(GGCX)
ACS: 100555036(ggcx)
PVT: 110072205(GGCX)
PBI: 103064362(GGCX)
GJA: 107120342(GGCX)
XLA: 444473(ggcx.L)
XTR: 100144666(ggcx)
NPR: 108786501(GGCX)
DRE: 557240(ggcx)
IPU: 108276729(ggcx)
AMEX: 103037933(ggcx)
TRU: 101067681(ggcx)
LCO: 104923320(ggcx)
NCC: 104944448(ggcx)
MZE: 101484617(ggcx)
OLA: 101172424(ggcx)
XMA: 102224466(ggcx)
PRET: 103473687(ggcx)
NFU: 107372879(ggcx)
CSEM: 103390489(ggcx)
LCF: 108879865(ggcx)
HCQ: 109513153(ggcx)
BPEC: 110160481(ggcx)
SASA: 106563193
ELS: 105014991(ggcx)
SFM: 108931977(ggcx)
LCM: 102360484(GGCX)
CMK: 103187831(ggcx)
CIN: 780874(ggcx)
SPU: 764318
APLC: 110974161
SKO: 102801874
DME: Dmel_CG13927(GC)
DSI: Dsimw501_GD13462(Dsim_GD13462)
MDE: 101889022
AAG: 110675715
AME: 551869(GC)
BIM: 100749841
BTER: 100645769
SOC: 105204060
AEC: 105149615
ACEP: 105624485
PBAR: 105421986
HST: 105191645
CFO: 105250361
LHU: 105675652
PGC: 109860098
NVI: 100123716
TCA: 659418
NVL: 108568265
PMAC: 106710934
PRAP: 110993504
PXY: 105388304
API: 100161672
DNX: 107166675
ZNE: 110828681
FCD: 110841759
TUT: 107364188
CRG: 105332560
OBI: 106881997
EPA: 110252598
ADF: 107336790
 » 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.
  Sequence
[hsa:2677]
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.
Reference
7  [PMID:22516721]
  Authors
Rishavy MA, Berkner KL
  Title
Vitamin K oxygenation, glutamate carboxylation, and processivity: defining the three critical facets of catalysis by the vitamin K-dependent carboxylase.
  Journal
Adv. Nutr. 3 (2012) 135-48.
Other DBs
ExplorEnz - The Enzyme Database: 4.1.1.90
IUBMB Enzyme Nomenclature: 4.1.1.90
ExPASy - ENZYME nomenclature database: 4.1.1.90
BRENDA, the Enzyme Database: 4.1.1.90

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