ライフサイエンスコーパス: Gla

1 Gla formation is thought to occur in two independent ste

2 Gla KO mice accumulated GL-3 in various tissues and flui

3 As long as 1 Gla residue remained on each side of Pro64, the ability

4 rings: Gla(3)-Gla(14)('), Gla(7)-Gla(10)('), Gla(10)-Gla(7)('), and Gla(14)-Gla(3)(').

5 la(3)-Gla(14)('), Gla(7)-Gla(10)('), Gla(10)-Gla(7)('), and Gla(14)-Gla(3)(').

6 merizing conantokin, i, i + 4, i + 7, i + 11 Gla spacing alone was shown to be insufficient for self-

7 llowing residue pairings: Gla(3)-Gla(14)('), Gla(7)-Gla(10)('), Gla(10)-Gla(7)('), and Gla(14)-Gla(3)

8 )-Gla(10)('), Gla(10)-Gla(7)('), and Gla(14)-Gla(3)(').

9 tween the following residue pairings: Gla(3)-Gla(14)('), Gla(7)-Gla(10)('), Gla(10)-Gla(7)('), and Gl

10 th con-G at 8 of 21 amino acids, including 4 Gla residues.

11 residue pairings: Gla(3)-Gla(14)('), Gla(7)-Gla(10)('), Gla(10)-Gla(7)('), and Gla(14)-Gla(3)(').

12 x-ray crystal structure of prothrombin as a Gla-domainless construct carrying an Ala replacement of

13 ombin is composed of fragment 1 containing a Gla domain and kringle-1, fragment 2 containing kringle-

14 2+) coordination/phospholipid binding) for a Gla residue in vitamin K-dependent proteins.

15 on three-dimensional solution structure of a Gla/Hyp-containing 18-residue conantokin, conRl-B, by hi

16 is that con-T contains a Lys, rather than a Gla, at position 7.

17 headgroup in the second site binds through a Gla domain-bound calcium ion Ca1, Gla30, and Lys11.

18 Alpha-galactosidase A (Gla) deficiency leads to widespread tissue accumulation

19 n, such as matrix gamma-carboxyglutamic acid Gla protein, fetuin, and osteopontin, also contribute to

20 acid residues to gamma-carboxyglutamic acid (Gla) by the vitamin K-dependent gamma-glutamyl carboxyla

21 mic acids in the gamma-carboxyglutamic acid (Gla) domain are carboxylated.

22 First, the gamma-carboxyglutamic acid (Gla) domain binds C6PS only in the absence of Ca(2+) (k(

23 utamic acid-rich gamma-carboxyglutamic acid (Gla) domain of factor IX is involved in phospholipid bin

24 occupancy by the gamma-carboxyglutamic acid (Gla) domain of protein C/APC leads to its dissociation f

25 K5 in factor IX gamma-carboxyglutamic acid (Gla) domain participates in binding endothelial cells/co

26 2+) sites in the gamma-carboxyglutamic acid (Gla) domain replaced by Mg(2+) at positions 1, 4, and 7.

27 a) consists of a gamma-carboxyglutamic acid (Gla) domain, two epidermal growth factor-like domains, a

28 PCR) through its gamma-carboxyglutamic acid (Gla) domain, with unknown hemostatic consequences in viv

29 of these encode gamma-carboxyglutamic acid (Gla) domain-containing proteins, which we have named Ci-

30 f the N-terminal gamma-carboxyglutamic acid (Gla) domain.

31 lserine (PS) via gamma-carboxyglutamic acid (Gla) domains is one of the essential steps in the blood

32 sess the role of gamma-carboxyglutamic acid (Gla) domains of FX and FIX in FVIIa/TF induced coagulati

33 lserine (PS) via gamma-carboxyglutamic acid (Gla) domains.

34 acing Asp14 with gamma-carboxyglutamic acid (Gla) increases the sharpness of pH response (transition

35 L-gamma-Carboxyglutamic acid (Gla) is an uncommon amino acid that binds avidly to mine

36 an extracellular gamma-carboxyglutamic acid (Gla) protein domain and cytosolic WW binding motifs.

37 The proline-rich gamma-carboxyglutamic acid (Gla) proteins (PRGPs) 1 and 2 are the founding members o

38 te transmembrane gamma-carboxyglutamic acid (Gla) proteins.

39 c positioning of gamma-carboxyglutamic acid (Gla) residues within the primary sequence of the peptide

40 ine-loop and two gamma-carboxyglutamic acid (Gla) residues, formed by post-translational modification

41 d analogues of l-gamma-carboxyglutamic acid (Gla), appropriately protected for Fmoc-based solid-phase

42 mate to generate gamma-carboxyglutamic acid (Gla).

43 nd glutamate to gamma-carboxy glutamic acid (Gla) residues in a number of specialized Gla-containing

44 At 45 weeks of age, Gla-deficient mice had developed more atherosclerosis th

45 divalent cation binding locus at Gla(11) and Gla(15).

46 ), Gla(7)-Gla(10)('), Gla(10)-Gla(7)('), and Gla(14)-Gla(3)(').

47 ombined deficiencies of apolipoprotein E and Gla.

48 th a substrate containing the propeptide and Gla domain of factor IX (FIXproGla41).

49 ure consisting of a predicted propeptide and Gla domain, a single-pass transmembrane segment, and tan

50 rtional increase in both tritium release and Gla formation occurred over a range of CO(2) concentrati

51 glutamate-containing conotoxins, Gla-TxX and Gla-TxXI, from the venom of Conus textile.

52 The protein C/APC Gla domain is implicated in both interactions.

53 e hypothesized that the unique protein C/APC Gla domain residues were responsible for mediating the s

54 e low-Mg(2+) condition, sEPCR binding to APC-Gla (or FVIIa-Gla) replaces Mg4 by Ca4 with an attendant

55 the primary divalent cation binding locus at Gla(11) and Gla(15).

56 The two calcium-binding Gla residues are located in a four residue N-terminal ex

57 llular matrix protein of the mineral-binding Gla protein family.

58 e (PtdSer): Gas6 lacking its PtdSer-binding 'Gla domain' is significantly weakened as a Tyro3/Mer ago

59 Osteocalcin (bone Gla protein) is an extracellular matrix protein synthesi

60 ication expressed alkaline phosphatase, bone Gla protein, and bone sialoprotein, suggesting an osteog

61 as FX(PCGla/EGF1) and FIX(PCGla/EGF1) (both Gla and EGF1 domains replaced with those of protein C).

62 -PZ), and a chimeric PZ mutant in which both Gla and EGF-like domains of the molecule were substitute

63 ain and intrachain metal ion coordination by Gla residues in similar locations.

64 We sought to identify how the protein C Gla domain enables specific protein-protein interactions

65 that are not shared with the human protein C Gla domain.

66 of N-terminal residues perturbed by calcium, Gla(2) and Ser(3), moves away from the His(8) and Trp(10

67 ino acids with three gamma-carboxyglutamate (Gla) residues, a post-translationally modified amino aci

68 antokin-G (con-G), a gamma-carboxyglutamate (Gla)-rich neuroactive peptide from a venomous marine sna

69 mino acid residues), gamma-carboxyglutamate (Gla)-rich peptide components of the venoms of marine sna

70 naturally occurring gamma-carboxyglutamate (Gla)-rich peptides that specifically antagonize the N-me

71 certain proteins to gamma-carboxyglutamate (Gla).

72 acids, particularly gamma-carboxyglutamate (Gla).

73 We prepared the fully carboxylated Gla domain of Factor IX by solid phase peptide synthesis

74 cids are Bu-Mal 2, BCAH 3, Pen-Mal 4, and Cm-Gla 5.

75 amma-carboxyglutamate-containing conotoxins, Gla-TxX and Gla-TxXI, from the venom of Conus textile.

76 kringle domain), to fragment 1.2 (containing Gla and the two kringle domains only) and to fragment 2

77 he result-ing synthetic peptide (Gla-Cys-Cys-Gla-Asp-Gly-Trp*-Cys-Cys-Thr*-Ala-Ala-Hyp-OH, where Trp*

78 13-amino acid glycopeptide tx5a (Gla-Cys-Cys-Gla-Asp-Gly-Trp*-Cys-Cys-Thr*-Ala-Ala-Hyp-OH, where Trp*

79 tionary emergence of the vitamin K-dependent Gla domain before the divergence of vertebrates and uroc

80 mma-carboxyglutamic acid domainless FXa (des-Gla-FXa), increasing its amidolytic activity.

81 en proposed based on modeling with human des-Gla-fXa.

82 presence of DEGR-FX or DEGR-FXa (but not des-Gla-DEGR-FXa), Ixolaris becomes a tight inhibitor of FVI

83 an N-terminal gamma-carboxyglutamate domain (Gla) followed by two kringles (K1 and K2).

84 These two proteins possess extracellular Gla domains with 13 or 9 potential Gla residues, respect

85 question by infusing a chimera of mouse FIX (Gla and EGF1) with FVIIa (EGF2 and catalytic domain) int

86 mic acid gamma,gamma'-tert-butyl ester (Fmoc-Gla(O(t)Bu)(2)-OH), a suitably protected analogue for Fm

87 al complex, the asymmetric synthesis of Fmoc-Gla(O(t)Bu)(2)-OH was completed in nine steps from thios

88 urochordates and suggest novel functions for Gla domain proteins distinct from their roles in vertebr

89 These findings suggest a new role for Gla residues and accompanying cation binding in the stab

90 antation from Gla-/0 to Gla+/0 mice and from Gla+/0 to Gla-/0 mice did not change the thrombotic phen

91 es the carboxylase to distinguish Glu's from Gla's.

92 Bone marrow transplantation from Gla-/0 to Gla+/0 mice and from Gla+/0 to Gla-/0 mice did

93 in the presence/absence of Mg(2+) to FVIIa, Gla-domainless FVIIa, and prothrombin fragment 1 support

94 ondition, sEPCR binding to APC-Gla (or FVIIa-Gla) replaces Mg4 by Ca4 with an attendant conformationa

95 not fiber, via an interaction between the FX Gla domain and hypervariable regions of the hexon surfac

96 nn Pick type C2 (Npc2), alpha-galactosidase (Gla), are up-regulated in early adipogenesis, and are tr

97 arboxylase converts Glu to carboxylated Glu (Gla) to activate a large number of vitamin K-dependent p

98 ions through gamma-carboxylated glutamates (Gla residues) and inhibits bone morphogenetic protein (B

99 uted these residues individually with Ala in Gla-domainless forms of recombinant factor IX expressed

100 our oxygen atoms, two from the side chain in Gla 24, and two from the side chain of Gla 21.

101 The histological changes in Gla KO mice better resemble the type 2 later-onset pheno

102 bstituted with Ala in separate constructs in Gla-domainless forms.

103 o determine if mice genetically deficient in Gla are susceptible to vascular thrombosis, a photochemi

104 a potent vascular prothrombotic phenotype in Gla-deficient mice and suggest that antithrombotic thera

105 approximately 45 amino acids that is rich in Gla.

106 he Factor IX Gla domain is different than in Gla domain structures of other vitamin K-dependent prote

107 between conRl-B and conG in the second inter-Gla loop was used to design analogues for structure-acti

108 A/K15A/S16A/N17A] (Ala/con-G, where gamma is Gla), in which all nonessential amino acids were altered

109 CR binding using 3 amino acid changes in its Gla domain (L4F/L8M/W9R).

110 is similar to the structure of the Factor IX Gla domain in the presence of calcium ions as determined

111 alcium coordination network of the Factor IX Gla domain is different than in Gla domain structures of

112 o those found in the calcium-bound factor IX Gla domain, FIX(1-47)-Ca(2+).

113 interactions are dependent on the factor IX Gla domain.

114 An anti-factor IX Gla monoclonal antibody was a potent inhibitor of factor

115 Our results suggest that factor IX Gla-domain mediated binding to endothelial cells/collage

116 alpha-Galactosidase A gene knockout (Gla KO) mice have no alpha-galactosidase A activity and

117 Notably, the new conantokins lack Gla at the 3rd position from the N terminus, where the G

118 utants of prethrombin-1 (prothrombin lacking Gla and Kringle-1 domains) in which basic residues of th

119 The simulations show larger Gla-EGF1 and EGF1-EGF2 inter-domain motions for FVII((IX

120 Matrix Gla protein (MGP) is a 14-kD extracellular matrix protei

121 Matrix Gla protein (MGP) is a potent inhibitor of vascular calc

122 Matrix Gla protein (MGP) is an antagonist of BMPs that is highl

123 Matrix Gla protein (MGP) is an inhibitor of vascular calcificat

124 about 18% mineral, 80% fetuin, and 2% matrix Gla protein (MGP) by weight, and the presence of the com

125 Osteocalcin (OC) and matrix Gla protein (MGP) are considered evolutionarily related

126 e mineral and the proteins fetuin and matrix Gla protein (MGP) that was initially discovered in serum

127 neral regulators osteonectin (ON) and matrix Gla protein (MGP).

128 calcification inhibitors fetuin-A and matrix Gla protein suggests a novel role for EVs in intercellul

129 e mineral and the proteins fetuin and matrix Gla protein that was initially discovered in the serum o

130 antagonists follistatin, noggin, and matrix Gla protein were expressed in cultured bovine and human

131 neralization, such as osteopontin and matrix Gla protein, but not osteocalcin, were concomitant to th

132 se, osteoprotegerin, osteopontin, and matrix Gla protein.

133 duced by extrahepatic tissues such as matrix Gla protein or osteocalcin.

134 or angiogenesis and is antagonized by matrix Gla protein (MGP) and crossveinless 2 (CV2), both induce

135 disease and is, in part, prevented by matrix Gla protein (MGP).

136 encing the inhibitor of calcification matrix Gla (MGP) in the trabecular meshwork cells.

137 pressed in the lymphatic endothelium (matrix Gla protein, apolipoprotein D precursor, and selenoprote

138 uggesting a prominent association for matrix Gla protein and osteopontin in ABCC6-related dystrophic

139 Mutations in matrix Gla protein (MGP) have been correlated with vascular cal

140 f BMP-2 and BMP-4; the BMP inhibitors matrix Gla protein (MGP) and Noggin; activin-like kinase recept

141 tion of the mineralization inhibitors matrix Gla protein and osteopontin.

142 Moreover, matrix Gla protein-depleted human aortic endothelial cells in v

143 sed on the basis of the properties of matrix Gla protein (MGP) as a vitamin K-dependent calcification

144 atenin signaling and/or inhibition of matrix Gla protein (MGP) carboxylation.

145 Here, we show that deficiency of matrix Gla protein (MGP), a BMP inhibitor, causes induction of

146 ontact also induced the expression of matrix Gla protein (MGP), a regulator of BMP function in the va

147 dothelium, resulting from the loss of matrix Gla protein (MGP), causes ectopic hepatic differentiatio

148 and a reduction in the expression of matrix Gla protein (MGP), osteopontin (OPN), and vascular calci

149 e cells in calcified blood vessels of matrix Gla protein deficient (MGP(-/-)) mice.

150 Enhancement of matrix Gla protein expression in Ins2Akita/+ mice, as mediated

151 ification, mice with gene deletion of matrix Gla protein, a bone morphogenetic protein (BMP)-inhibito

152 have abundant uncarboxylated form of matrix Gla protein, which allowed progressive tissue mineraliza

153 s critical VKD proteins [osteocalcin, matrix Gla protein (Mgp), growth arrest specific protein 6, tra

154 ification inhibitors osteoprotegerin, matrix Gla protein, and osteopontin.

155 apolipoprotein E, vitamin D receptor, matrix Gla protein, peroxisome proliferator activated receptor

156 by loss-of-function mutations in the matrix Gla protein (MGP) gene.

157 related to loss of regulation of the matrix Gla protein.

158 wth factor 23 (FGF23), uncarboxylated matrix Gla protein (ucMGP), and fetuin-A are regulators of mine

159 notably found that undercarboxylated matrix Gla protein precisely colocalized within areas of minera

160 on, OPN mutant mice were crossed with matrix Gla protein (MGP) mutant mice.

161 This emerging family of integral membrane Gla proteins includes proline-rich Gla protein (PRGP) 1,

162 els for proteomics, PEDRo and our own model (Gla-PSI-Glasgow Proposal for the Proteomics Standards In

163 In this model, Gla-/0 mice displayed a progressive age-dependent shorte

164 hesized to evaluate the contributions of non-Gla residues to conantokin self-association.

165 d more atherosclerosis than mice with normal Gla expression (25.1+/-14.0 versus 12.3+/-9.3 mm2 of tot

166 whereas sphingosine inhibited activation of Gla-domainless prothrombin by factor Xa/factor Va in the

167 at an i, i + 4, i + 7, i + 11 arrangement of Gla residues is essential for con-G self-assembly.

168 on an "i, i + 4, i +7, i +11" arrangement of Gla residues, as occurs in native con-G.

169 mbent upon intermolecular Ca(2+) bridging of Gla residues spaced at i, i + 4, i + 7, i + 11 intervals

170 in in Gla 24, and two from the side chain of Gla 21.

171 d, in addition to a high relative content of Gla, contains a hexapeptide disulfide loop between Cys r

172 These findings suggest that deficiency of Gla leads to increased inducible nitric oxide synthase e

173 the membrane, where the combined effects of Gla-Gla interaction, template bridging, and interaction

174 n the small intestine and sensory ganglia of Gla KO mice provides a model for study of enteropathy an

175 TFPI and K1K2C are worse inhibitors of Gla-domainless factor Xa, compared to wild-type factor X

176 pH values consistent with the ionization of Gla carboxylate groups.

177 illustrate the multifunctional potential of Gla domains.

178 ow Mg(2+), reexamination of the structure of Gla domain of activated Protein C (APC) complexed with s

179 of PZ, we determined the x-ray structure of Gla-domainless PZ (PZ(DeltaGD)) complexed with protein Z

180 thology of young to old (3 to 17 months old) Gla KO mice and compare these changes with those in stra

181 (K7 gamma), two peptides that harbor optimal Gla spacing, was established.

182 nverts Glu's to gamma-carboxylated Glu's, or Gla's, in the Gla domain.

183 find that loss of membrane binding and other Gla-dependent functions in the substrate leads to a decr

184 tion between the following residue pairings: Gla(3)-Gla(14)('), Gla(7)-Gla(10)('), Gla(10)-Gla(7)('),

185 imilar studies with fXa-des-EGF-1 and fXa/PC-Gla suggested that protein-protein interaction with eith

186 ontained the Gla domain of protein C (fXa/PC-Gla).

187 placement mutants: FX(PCGla) and FIX(PCGla) (Gla domain replaced with that of protein C), FX(PCEGF1)

188 While the result-ing synthetic peptide (Gla-Cys-Cys-Gla-Asp-Gly-Trp*-Cys-Cys-Thr*-Ala-Ala-Hyp-OH

189 Using positional Gla variants of conantokin-R (con-R), a non-dimerizing c

190 f known MGPs, and it contains seven possible Gla residues that would make the sturgeon protein the mo

191 acellular Gla domains with 13 or 9 potential Gla residues, respectively, followed by membrane-spannin

192 The human prothrombin Gla domain, which cannot bind EPCR or support protein S

193 mented the heparin acceleration by relieving Gla domain inhibition as previously shown for heparin br

194 ynthetic peptide analogues of the 47-residue Gla domain/helical stack of PC.

195 ng the gamma-carboxy glutamic acid residues (Gla domain) and the protease domain of factor IX.

196 membrane Gla proteins includes proline-rich Gla protein (PRGP) 1, PRGP2, TMG3, and TMG4, all of whic

197 Proline-rich Gla protein 2 (PRGP2) is one of four known vertebrate tr

198 rane and cytoplasmic regions of proline-rich Gla protein 2.

199 prothrombin gamma-carboxyglutamic acid-rich (Gla) domain is important in membrane binding.

200 N-terminal gamma-carboxyglutamic acid-rich (Gla) domain, a membrane-anchoring domain found on vitami

201 which converts Glu's to carboxylated Glu's (Gla's) in their Gla domains.

202 Appropriately spaced Gla residues allow binding of functional divalent cation

203 id (Gla) residues in a number of specialized Gla-containing proteins.

204 These results reveal the specific Gla domain residues responsible for mediating protein C/

205 odies are directed at the calcium-stabilized Gla domain and interfere with Factor IX-membrane interac

206 has three linkers connecting the N-terminal Gla domain to kringle-1 (Lnk1), the two kringles (Lnk2),

207 dular assembly that comprises the N-terminal Gla domain, kringle-1, kringle-2, and the C-terminal pro

208 gle-2/protease domain pair on the N-terminal Gla domain/kringle-1 pair anchored to the membrane.

209 han-M requires calcium binding to N-terminal Gla residues, where presumably histidine and tryptophan

210 ated CK2 site at Thr37 within the N-terminal Gla-domain.

211 after proteolytic removal of the N-terminal Gla-K1 region of F12.

212 f factor Xa equally, suggesting a C-terminus/Gla domain interaction.

213 The Gla domain of factor Xa was not required for myosin's pr

214 The Gla residues were also required for BMP-4 binding but fl

215 2) The Gla domain plays an allosteric role in substrate-enzyme

216 Moreover, patients' IgG directed against the Gla domain inhibited the binding of factor IX to phospho

217 ed positioning of a small substrate, and the Gla domain is not sterically constrained by the rest of

218 rupts interactions between factor Va and the Gla domain of factor Xa in the prothrombinase complex.

219 mutagenesis was used to modify Pro64 and the Gla residues, and the effect on BMP-4 activity, and bind

220 s within 9 A of the protease domain, and the Gla-domain primed for membrane binding comes in contact

221 ains of the protease (E2-fXa) as well as the Gla and both kringle domains of the substrate (prethromb

222 and (ii) a specific interaction between the Gla domains of PZ and fXa contributes approximately 6-fo

223 ck either the Gla domain (GD-fX) or both the Gla and EGF-1 domains (E2-fX).

224 ves of fXa and prothrombin in which both the Gla and first EGF-like domains of the protease (E2-fXa)

225 is reduced 3-fold by FLEEL and 9-fold by the Gla domain (residues 1-46) of FIX.

226 her hypothesized that calcium binding by the Gla residues is a prerequisite for BMP inhibition.

227 endothelial protein C receptor (EPCR) by the Gla-domain of protein C/APC is responsible for the beta-

228 ess a chimeric protein (F9CH) comprising the Gla domain of factor IX fused to the transmembrane and c

229 domain (fXa-des-EGF-1), or 3) contained the Gla domain of protein C (fXa/PC-Gla).

230 ic activated protein C mutant containing the Gla domain of fXa was susceptible to inhibition by ZPI i

231 fX and its two mutants which lack either the Gla domain (GD-fX) or both the Gla and EGF-1 domains (E2

232 protein-protein interaction with either the Gla or the EGF-1 domain may not play a dominant role in

233 xception of a basic recognition site for the Gla domain of fX, no other interactive site on TF for th

234 al that alternate interactions exist for the Gla domain of protein C such that it is comparable with

235 synthetic 13-residue "postpeptide" from the Gla-TxXI precursor reduced the K(m) for the reaction of

236 Select mutations in the Gla and protease domains of recombinant APC caused a los

237 th an attendant conformational change in the Gla domain omega-loop.

238 o gamma-carboxylated Glu's, or Gla's, in the Gla domain.

239 FVIIa binds seven Ca(2+) ions in the Gla, one in the EGF1, and one in the protease domain.

240 th residue substitutions introduced into the Gla, thrombin-sensitive region (TSR), epidermal growth f

241 d to prethrombin I (the fragment lacking the Gla domain and the first kringle domain), to fragment 1.

242 addition, we characterized the effect of the Gla domain and carboxylation on propeptide and substrate

243 to accommodate the hydrophobic patch of the Gla domain consisting of Leu-6, Phe-9, and Val-10.

244 tudied extensively; however, the role of the Gla domain in substrate binding is less well understood.

245 The overall structure of the Gla domain in the Factor IX-(1-47)-antibody complex at 2

246 (M84R-FXa) also reveals the structure of the Gla domain in the presence of Mg(2+).

247 The Ca(2+)-stabilized structure of the Gla domain is not required for F12 to bind the zymogen f

248 ecognizes the calcium-stabilized form of the Gla domain of Factor IX.

249 E2-fXa revealed that the interaction of the Gla domain of fXa with PCPS also induces conformational

250 e Gla domain as well as sites outside of the Gla domain of protein C/APC.

251 To investigate the binding of the Gla domain of prothrombin fragment 1 (PT1) to anionic li

252 o interact with either the C-terminus of the Gla domain or the EGF-1 domain of fX.

253 tic Ser-525 and requires the presence of the Gla domain.

254 This phenomenon is also independent of the Gla domain.

255 aising questions about the importance of the Gla for this reaction.

256 KS region may also facilitate exiting of the Gla product from the catalytic center by ionic attractio

257 nal response to C6PS requires linkage of the Gla, EGF(NC), and catalytic domains in the presence of C

258 esidues perturbed gamma-carboxylation of the Gla-TxXI peptide.

259 or Xa and that this interaction required the Gla domain.

260 In this structure, the Gla domain has four Ca(2+) and three bound Mg(2+).

261 a molecular framework demonstrating that the Gla and EGF1 domains of FX interact more strongly with F

262 inhibition of FVIIa/TF and implies that the Gla domain is necessary for FVIIa/TF/Ixolaris/FX(a) comp

263 We found that the Gla domain is tightly associated with the carboxylase du

264 We recently demonstrated that the Gla domain-dependent interaction of protein C with endot

265 , zebrafish factor VII demonstrates that the Gla-EGF-EGF-SP domain structure, which is common to coag

266 (65)Zn(2+) revealed that Zn(2+) bound to the Gla domain as well as sites outside of the Gla domain of

267 are linked by Ca(2+) and C6PS binding to the Gla domain.

268 3rd position from the N terminus, where the Gla residue is replaced by either aspartate or by anothe

269 the reaction via their propeptide, while the Gla domain undergoes intramolecular movement to repositi

270 of the sTF subdomain that interacts with the Gla and EGF1 domains of VIIa; neither Glu(84) nor Thr(12

271 inantly located on the cell surface with the Gla domain exposed extracellularly.

272 which does not require interaction with the Gla domain of FX, recruits PAR-1 to protective signaling

273 It also suggests that residues within the Gla and EGF1 domains of protein S act cooperatively for

274 ther additional interaction sites within the Gla domain of protein S might contribute to its APC cofa

275 Thus, intramolecular movement within the Gla domain to reposition new Glu's for catalysis is as r

276 induces structural perturbations within the Gla-containing N terminus and the Cys(11)-Cys(5)-Pro(6)

277 Glu's to carboxylated Glu's (Gla's) in their Gla domains.

278 These Gla analogues have been designed to replace the glutamic

279 The remaining three Gla domain proteins are similar to proteins that partici

280 The three Gla residues project from the same face of the helical t

281 Bone marrow transplantation from Gla-/0 to Gla+/0 mice and from Gla+/0 to Gla-/0 mice did not chang

282 rom Gla-/0 to Gla+/0 mice and from Gla+/0 to Gla-/0 mice did not change the thrombotic phenotype of t

283 activity, clusters of Glu's are converted to Gla's, and fully carboxylated VKD proteins are normally

284 expressed in CHO cells and is homologous to Gla-RTK, a putative receptor tyrosine kinase previously

285 min K-dependent proteins, converting them to Gla-containing proteins.

286 contribution of the hexapeptide loop toward Gla domain structure and function was evaluated using wi

287 cDNAs for two additional human transmembrane Gla proteins (TMG) of 20-24 kDa named TMG3 and TMG4.

288 The 13-amino acid glycopeptide tx5a (Gla-Cys-Cys-Gla-Asp-Gly-Trp*-Cys-Cys-Thr*-Ala-Ala-Hyp-OH

289 n of the distances between the uncoordinated Gla oxygen atoms is with the intercalcium distance of 9.

290 and that zebrafish MGP, which lacks upstream Gla residues, did not function as a BMP inhibitor.

291 107 nm, whereas factor IX with a factor VII Gla domain (rFIX/VII-Gla) and factor IX expressed in the

292 ble (200 and 150 units/mg), whereas rFIX/VII-Gla activity was low (<2 units/mg).

293 d that the poor activity of zymogen rFIX/VII-Gla was caused by a specific defect in activation by fac

294 or IX with a factor VII Gla domain (rFIX/VII-Gla) and factor IX expressed in the presence of warfarin

295 complex shows that all four domains of VIIa (Gla, EGF-1, EGF-2, and protease) are in contact with TF.

296 inant factor IXabeta and activated rFIX/VIIa-Gla had similar activities (80 and 60% of plasma factor

297 ine did not inhibit thrombin generation when Gla-domainless factor Xa was used in prothrombinase assa

298 To determine whether Gla affects the progression of atherosclerosis, mice wer

299 cterized in amidolytic assays performed with Gla-domainless factor Xa and in prothrombin activation a

300 demonstrated interaction of the fXa and ZPI Gla domains, resulted in an additional approximately 100