ライフサイエンスコーパス: kringle

1 lysine-binding site interaction with a Pg/Pm kringle.

2 contains structural domains that are termed kringles.

3 lysine-binding site (LBS) found in other Pgn kringles.

4 otions of the backbone nitrogen atoms of the kringle 1 domain of human plasminogen (K1(Pg)) were exam

5 generated a targeted genetic deletion in the kringle 1 domain of zebrafish prothrombin.

6 brafish and provide insight into the role of kringle 1 in prothrombin maturation and activity.

7 When kringle 1 is removed from kringle 1-3, the resulting kri

8 This implies that kringle 1, although virtually ineffective in inhibiting

9 c plasma contained 2.9-fold more plasminogen kringle 1-3 fragments (angiostatin) than that in control

10 migration, may influence the conformation of kringle 1-3 to alter its anti-migratory activity.

11 When kringle 1 is removed from kringle 1-3, the resulting kringle 2-3 becomes more pote

12 sulting kringle 2-3 becomes more potent than kringle 1-3.

13 Mouse angiostatin (kringle 1-4) and endostatin were expressed in yeast.

14 ringle domains tested, including plasminogen kringle 1.

15 bs: a linear epitope within a domain linking kringles 1 and 2; a nonlinear epitope contained within t

16 nic, hydrophobic, cationic) like plasminogen kringles 1 and 4.

17 A fragment of plasminogen containing kringles 1 through 3 also bound to TF apoprotein, wherea

18 t of plasmin autoproteolysis and consists of kringles 1 to 4 and approximately 85% of kringle 5.

19 Plasminogen, plasmin, and AS4.5 all contain kringles 1 to 4; however, kringle 5 is truncated in AS4.

20 ents demonstrated that both the N domain and kringles 1-2 bind the beta-chain moiety (amino acid resi

21 ggregation, indicating the important role of kringles 1-3 for plasmin interactions with these cells.

22 A plasminogen fragment containing kringles 1-3 inhibited the enzymatic activity of scuPA/s

23 high affinity through an interaction between kringles 1-3 of Pg and the extracellular domain of TF.

24 Proteolytic cleavage of plasminogen yields kringles 1-3 or 4 and kringle 5 (K5), which regulate end

25 The receptor for kringles 1-3 or 4 has been identified as cell surface-as

26 We show that kringles 1-4, but not kringles 1-3, bind the CI-MPR, indicating an essential r

27 ere the bowl-shaped structure of angiostatin kringles 1-3, the first multi-kringle structure to be de

28 ibitory effects of EACA: mini-Pg which lacks kringles 1-4 of Glu-Pg and micro-Pg which lacks all krin

29 giostatin isoform, consisting of plasminogen kringles 1-4 plus 85% of kringle 5 (amino acids Lys78 to

30 Pg, Lys-Pg (des(1-77)), and Mini-Pg (lacking kringles 1-4) bound Fn with K(d) values of 3.1, 0.21, an

31 We show that kringles 1-4, but not kringles 1-3, bind the CI-MPR, ind

32 kers connecting the N-terminal Gla domain to kringle-1 (Lnk1), the two kringles (Lnk2), and kringle-2

33 mation where the distance between Ser-101 in kringle-1 and Ser-210 in kringle-2 increases by 13 A.

34 here the domains are not vertically stacked, kringle-1 comes within 9 A of the protease domain, and t

35 f prethrombin-1 (prothrombin lacking Gla and Kringle-1 domains) in which basic residues of this site

36 thrombin uses the intramolecular collapse of kringle-1 onto the active site in the closed form to pre

37 ipated intramolecular collapse of Tyr(93) in kringle-1 onto Trp(547) in the protease domain that obli

38 ase domain pair on the N-terminal Gla domain/kringle-1 pair anchored to the membrane.

39 kringles suggests multiple arrangements for kringle-1 relative to the rest of the prothrombin molecu

40 r (Lnk2) composed of 26 amino acids connects kringle-1 to kringle-2 in the coagulation factor prothro

41 ed of fragment 1 containing a Gla domain and kringle-1, fragment 2 containing kringle-2, and a protea

42 ly that comprises the N-terminal Gla domain, kringle-1, kringle-2, and the C-terminal protease domain

43 al turn, bind within the bipolar angiostatin kringle 2 (K2) domain lysine-binding site.

44 plasminogen (hPg) and plasmin (hPm) via the kringle 2 (K2hPg) domain of hPg/hPm and the N-terminal a

45 ous studies revealed that, by binding to the kringle 2 (KR2) domain of host Plg, the pathogen attains

46 ecule of crystallization while the former of kringle 2 and kringle 3 are cofacial.

47 Moreover, the separation of the kringle 2 and kringle 3 lysiner binding sites is suffici

48 tern D GAS is fully recapitulated by the hPg kringle 2 domain (K2hPg) and a short internal peptide re

49 , thus localizing the cognate epitope to the kringle 2 domain in prothrombin.

50 tight and highly specific interaction of the kringle 2 domain of human plasminogen (K2(Pg)) with a 30

51 of human matrix metalloproteinase-2 and the kringle 2 domain of human plasminogen, of 60 and 83 amin

52 1 is removed from kringle 1-3, the resulting kringle 2-3 becomes more potent than kringle 1-3.

53 alculated for two protein domains, col 2 and kringle 2.

54 f the 30 residue peptide VEK-30 found in the kringle 2/VEK-30 complex.

55 ity for the lysine binding site (LBS) of the kringle-2 (K2) domain of human (h)Pg.

56 cture of a complex of a modified recombinant kringle-2 domain of human plasminogen, K2Pg[C4G/E56D/L72

57 osed of 26 amino acids connects kringle-1 to kringle-2 in the coagulation factor prothrombin.

58 between Ser-101 in kringle-1 and Ser-210 in kringle-2 increases by 13 A.

59 ed that the A-domain of PAM binds to the hPg kringle-2 module (K2(hPg)), but how this relates to the

60 is located in a disordered region connecting kringle-2 to the A chain, but Arg-320 is well defined wi

61 ingle-1 (Lnk1), the two kringles (Lnk2), and kringle-2 to the C-terminal protease domain (Lnk3).

62 domain and kringle-1, fragment 2 containing kringle-2, and a protease domain containing A and B chai

63 prises the N-terminal Gla domain, kringle-1, kringle-2, and the C-terminal protease domain connected

64 d for membrane binding comes in contact with kringle-2.

65 rent orientations by pivoting the C-terminal kringle-2/protease domain pair on the N-terminal Gla dom

66 Human plasminogen kringle 3 (hPgn K3) domain contains most elements of the

67 allization while the former of kringle 2 and kringle 3 are cofacial.

68 missense mutation p.Lys330Glu (K330E) in the kringle 3 domain of the PLG protein.

69 oreover, the separation of the kringle 2 and kringle 3 lysiner binding sites is sufficient to accommo

70 hin each of its five kringle domains, except kringle 3.

71 bind Pg 2 in the absence of CD26 via the Pg kringle 4 (K4) domain.

72 Apo(a) contains 14-37 kringle 4 (KIV) repeats distributed into 10 classes (1-1

73 lso bound to TF apoprotein, whereas isolated kringle 4 and miniplasminogen did not.

74 s closest homologue tetranectin binds to the kringle 4 domain of plasminogen and enhances its associa

75 rotein(a) [Lp(a)] are highly homologous with kringle 4 of plasminogen (75-94%) and like the latter ar

76 indicating an essential role for the LBS in kringle 4 of plasminogen.

77 ated lysine residues that were recognized by kringle 4 of the host protein.

78 indicated that binding of SK Lys(414) to Pg kringle 4 plays a role in recognition of Pg by SK.

79 n, subjects with small apo(a) size of <or=22 kringle 4 repeats had significantly lower FMD than those

80 ains multiple repeats resembling plasminogen kringle 4, is considered a risk factor for the developme

81 Kringle 4, which has only marginal anti-proliferative ac

82 e and was blocked by plasminogen/angiostatin kringle 4.

83 rial and plasma membrane protein) bound with kringle 5 (a peptide derived from the excess plasminogen

84 ting of plasminogen kringles 1-4 plus 85% of kringle 5 (amino acids Lys78 to Arg529).

85 The ligand binding properties of the kringle 5 (K5) domain of human plasminogen have been inv

86 Kringle 5 (K5) of human plasminogen has been shown to in

87 Kringle 5 (K5) of human plasminogen is a potent angiogen

88 IGN AND An expression plasmid of plasminogen kringle 5 (K5), a natural angiogenic inhibitor, was enca

89 n that intravitreal injection of plasminogen kringle 5 (K5), a potent angiogenic inhibitor, inhibits

90 of plasminogen yields kringles 1-3 or 4 and kringle 5 (K5), which regulate endothelial cell prolifer

91 Recombinant plasminogen kringle 5 (rK5) has been shown to induce apoptosis of de

92 s induce Ca(2+) signaling cascades; however, kringle 5 acts through voltage-dependent anion channel a

93 In this study, we demonstrate that kringle 5 binds to a region localized in the N-terminal

94 Isolated kringle 5 binds to actin, suggesting intact kringle 5 is

95 A molecular model of the SK.kringle 5 complex identifies the putative interactions i

96 2; a nonlinear epitope contained within the kringle 5 domain and the latent protease domain; and a n

97 e bonds and up to three peptide bonds in the kringle 5 domain of the protein.

98 o cell surface beta-actin, and the truncated kringle 5 in AS4.5 results in its release from beta-acti

99 can potentiate the antiangiogenic effects of Kringle 5 in endothelial cells.

100 We show that kringle 5 inhibits 1-LN cell proliferation and promotes

101 Furthermore, we also show that Pg kringle 5 is a substrate for the NADH-dependent reductas

102 kringle 5 binds to actin, suggesting intact kringle 5 is necessary for plasminogen and plasmin to bi

103 AS4.5 all contain kringles 1 to 4; however, kringle 5 is truncated in AS4.5.

104 r Fn cofactor activity, and (b) suggest that kringle 5 localizes and stabilizes Pg within the tPA-Fn

105 tion of [Lys]Pg and mini-Pg (containing only kringle 5 of Pg) by SK with Ala substitutions of Arg(253

106 57) mediate Pg substrate recognition through kringle 5 of the [Lys]Pg and mini-Pg substrates.

107 , mutation of the lysine binding site within kringle 5 of the plasminogen molecule also reduced the n

108 otein 78 have been identified as plasminogen kringle 5 receptors on endothelial cells.

109 se induce a conformational change in reduced kringle 5 that leads to attack by the Cys(541) thiolate

110 ands the range of ligands that interact with kringle 5 while it widens the scope of potential biologi

111 oes autoproteolysis within the inner loop of kringle 5, which can be induced by a free sulfhydryl don

112 l surface VDAC is a receptor for plasminogen kringle 5, which promotes partial closure of the channel

113 ional lysine binding site within plasminogen kringle 5.

114 tage-dependent anion channel, in addition to kringle 5.

115 of kringles 1 to 4 and approximately 85% of kringle 5.

116 teraction between the SK beta domain and Plg kringle 5.

117 beta domain additionally interacts with Plg kringle 5.

118 comprising the human endostatin gene and the kringle-5 domain of the human plasminogen gene (E::K-5)

119 with a lentivirus containing an endostatin::kringle-5 fusion gene demonstrated an inhibition of neov

120 Administration of anti-kringle Abs diminished LPS-induced up-regulation of uPA

121 chanism in which SK Lys(414) binding to a Pm kringle accompanies near-diffusion-limited encounter com

122 roduced a bifunctional A11-plasminogen first kringle agent (SLK), which homes to newly deposited fibr

123 Within uPA, both the kringle and proteolytic domains are recognized by alpha(

124 e recognition is also LBS-dependent, but the kringle and SK structural element(s) responsible have no

125 ding site (LBS) interactions between a Pg/Pm kringle and the SK COOH-terminal Lys(414).

126 distinct domains (containing Frizzled-like, kringle and tyrosine kinase motifs) indicates that these

127 s 1-4 of Glu-Pg and micro-Pg which lacks all kringles and contains only the catalytic domain.

128 ctive removal of its constituent Gla domain, kringles and linkers reveals their long-range communicat

129 tributed to its main structural domains, the kringles, and have been proposed to be mediated by their

130 which the addition of either a specific anti-kringle antibody or L-lysine abolished the interaction.

131 A, indicating that that the structure of the kringle as well as its interaction with the GFD govern r

132 polipoprotein(a) (apo(a); the distinguishing kringle-containing component of Lp(a)) elicits cytoskele

133 y, proteolysis of plasmin generates inactive kringle-containing fragments expressing angiostatic prop

134 somatotropin hormones, serpins, and various kringle-containing proteins.

135 lycerol had a long tail, in which individual kringles could be distinguished, extending from the ring

136 A scuPA variant lacking the kringle (Delta K-scuPA) bound to soluble uPAR (suPAR) wi

137 x formation and substrate binding, through a kringle-dependent mechanism.

138 respectively, whereas Micro-Pg (lacking all kringles) did not bind.

139 nce (residues 43-49) between the GFD and the kringle displayed a lower affinity for uPAR, were unable

140 al rabbit mAb in complex with the human ROR2 kringle domain (hROR2-Kr) guided affinity maturation by

141 actions between the N- domain and the second kringle domain (K2).

142 hil activation through interactions with its kringle domain (KD).

143 uPA receptor binding growth factor domain or kringle domain (kringle) from full-length single chain u

144 omains comes from its binding to plasminogen kringle domain 4 and to miniplasminogen (kringle domain

145 with the lysine-binding sites in plasminogen kringle domain 4 because a deletion mutant of plasminoge

146 gen kringle domain 4 and to miniplasminogen (kringle domain 5 plus the protease domain) with apparent

147 plasminogen kringle domains 1-4 and most of kringle domain 5, dose dependently reduces cell number d

148 Here, we show that cleavage of the kringle domain at Lys317/Thr318 switches its function to

149 bility of rFII to that of hFII, and the rFII kringle domain changed the stability of hFII to that of

150 The presence of the hFII kringle domain changed the stability of rFII to that of

151 CA), indicating the requirement for a lysine-kringle domain interaction.

152 lar analysis revealed that the extracellular Kringle domain is required for ROR1/ROR2 heterooligomeri

153 ichiometry in which the N-terminal and first kringle domain of HGF/SF contact the face of the seven-b

154 ids in the heparin binding site (HBS) in the kringle domain were mutated to alanines behaved like Del

155 ease domain, interactions between SK and the kringle domain(s) play a key role in Pg activation.

156 ragment lacking the Gla domain and the first kringle domain), to fragment 1.2 (containing Gla and the

157 Here we report the NMR structure of its kringle domain, NT/K.

158 proteoglycan NG2 with human plasminogen and kringle domain-containing plasminogen fragments have bee

159 in nucleolin through a region containing the kringle domain.

160 points toward a novel functional role for a kringle domain.

161 HGF containing the N-terminal and the first kringle domain.

162 nuclei through a mechanism that requires its kringle domain.

163 verified specific interaction of recMoPrP to kringle domains (K(1+2+3)) with higher binding by recMoP

164 xpressed the N-terminal (N) domain, the four kringle domains (K1 to K4) and the serine proteinase hom

165 Three kringle domains (K1, K2 and K4) displayed agonistic acti

166 s composed of an alpha-chain containing four Kringle domains (K1-K4) and a serine protease domain-lik

167 The N-terminal and first Kringle domains (NK1) of HGF comprise a naturally occurr

168 in containing an N-terminal segment and four kringle domains (NK4) antagonize HGF activity.

169 pigment epithelium-derived factor (PEDF) or Kringle domains 1-3 of angiostatin (K1K3) in reducing ab

170 g ulcers to a number of fragments, including kringle domains 1-3, an angiostatin-related protein.

171 d to angiostatin, which contains plasminogen kringle domains 1-3.

172 ring human isoform consisting of plasminogen kringle domains 1-4 and most of kringle domain 5, dose d

173 rably to plasminogen, which consists of five kringle domains and a serine protease domain, and to ang

174 uch as lysine analogs, bind unselectively to kringle domains and are therefore unsuitable for functio

175 cifically bound to alphavbeta(3) through the kringle domains and induced migration of endothelial cel

176 Additional evidence for NG2 interaction with kringle domains comes from its binding to plasminogen kr

177 ver, the lysine-binding sites in plasminogen kringle domains facilitate the C4BP-plasminogen interact

178 aracterize the roles of the different apo(a) kringle domains in in vitro assays.

179 Functional divergence among kringle domains is discussed on the basis of their surfa

180 lecules that specifically bind to the apo(a) kringle domains KIV-7, KIV-10, and KV.

181 Our data suggest that different kringle domains may contribute to the overall anti-angio

182 and the first kringle (K1) or the first two kringle domains of HGF.

183 ation was dependent on an interaction of the kringle domains of plasmin with alpha(9)beta(1) as well

184 Angiostatin, representing the kringle domains of plasmin, alone did not induce the mig

185 rotease (E2-fXa) as well as the Gla and both kringle domains of the substrate (prethrombin-2) had bee

186 to fragment 1.2 (containing Gla and the two kringle domains only) and to fragment 2 but not to throm

187 otease SK x Pg*, and we examined whether the kringle domains regulate this process.

188 ectivity for KIV-10, compared with the other kringle domains tested, including plasminogen kringle 1.

189 n inhibitor of angiogenesis, contains 3 to 4 kringle domains that are derived from proteolytic cleava

190 t the SK alpha domain binds avidly to the Pg kringle domains that maintain Glu-Pg in a tightly folded

191 The structure also shows that Pg kringle domains undergo significant structural rearrange

192 binding affinity and binding specificity of kringle domains with various ligands.

193 HGF/SF comprised of the N-terminal and first Kringle domains) by titration with either heparin or DS

194 s, the lysine binding sites on plasminogen's kringle domains, and plasmin's serine protease domain gr

195 ), which are located within each of its five kringle domains, except kringle 3.

196 asminogen fragment containing 3-4 N-terminal kringle domains, is a potent inhibitor of tumor-induced

197 s much slower in Glu-Pg, which contains five kringle domains, than in Pg forms containing one kringle

198 scope of potential biological functions for kringle domains.

199 ormation of Pg through interactions with the kringle domains.

200 of SK x Pg*, and this process is governed by kringle domains.

201 om release of both the variable and constant kringle domains.

202 ructural makeup from a composite of multiple kringle domains.

203 pecific for plasminogen and conserved in its kringle domains.

204 for functional characterization of specific kringle domains.

205 3:2 ratio, with the distance between the two kringles either fully extended (54 +/- 2 A) or partially

206 binding of SK Lys414 to [Lys]Pg and [Lys]Pm kringles enhances SK.[Lys]Pg* and SK.[Lys]Pm catalytic c

207 tional extracellular protein modules such as Kringle, epidermal growth factor, and Apple domains.

208 Several observations indicated the kringle facilitates the binding of uPA to uPAR.

209 distinguishes NT/K from other members of the kringle fold and points toward a novel functional role f

210 NT/K adopts the kringle fold, consisting of an antiparallel beta-sheet b

211 uences from different vertebrates, including kringles from hedgehog apolipoprotein(a) [Apo(a)] and Ap

212 ding growth factor domain or kringle domain (kringle) from full-length single chain uPA markedly atte

213 pression of a cDNA encoding a secreted, four-kringle human angiostatin inhibited tumor growth of B16F

214 1 domain of factor XI, we conclude that the Kringle II domain of prothrombin competes with HK for bi

215 and that this interaction occurs through the kringle II domain of prothrombin.

216 e data demonstrate an important role for the kringle in stabilizing the binding of scuPA to uPAR.

217 ragments were used to assess the role of the kringles in mediating the inhibitory effects of EACA: mi

218 th factor domains in protein C as opposed to kringles in prothrombin likely accounts for the differen

219 a novel, covalent binding by Lp(a) which is kringle independent and is postulated to involve the pse

220 ts that lysine binding sites are involved in kringle interaction with NG2.

221 sostructural, indicating that the LBS of the kringles is preformed anticipating ligand binding.

222 s were utilized: 8K-apo(a) mice expressing 8 kringle IV (KIV) repeats with a single copy of KIV-2; 8K

223 Apo(a) consists of 10 kringle IV domains (KIVs), one kringle V domain, and an

224 NaCl, but only by 30% in the case of the 15 kringle IV Lp(a) studied.

225 netically imputed Lp(a) molar concentration, kringle IV type 2 (KIV-2) repeats (which determine apo(a

226 els and/or corresponding LPA risk genotypes (kringle IV type 2 [KIV-2]) repeat polymorphism, rs379822

227 otein(a) isoform size with a genetic method (kringle IV type 2 [KIV2] repeats in the LPA gene) and a

228 g LPA risk genotypes (rs10455872, rs3798220, kringle IV type 2 repeat polymorphism) prospectively ass

229 (corresponding approximately to 22 or fewer kringle IV type 2 repeats vs. >22 repeats or analogously

230 We also measured copy numbers of kringle IV-2 (KIV-2) in LPA using qPCR.

231 The number of apolipoprotein (a) kringle IV-2 repeats was inversely related to Lp(a) mass

232 ith Lp(a) levels, but not with the number of kringle IV-2 repeats.

233 19 bond located in the linker region between kringles IV-4 and IV-5, a bond immediately upstream of t

234 olecular weight (LMW) apo(a) isoforms (</=22 Kringle-IV repeats) predicted ASCVD events (relative haz

235 h measurements of plasma lipoprotein(a), LPA kringle-IV type 2 number of repeats, and LPA rs10455872.

236 series of domains homologous to plasminogen kringle (K) 4, each of which possesses a potential lysin

237 ich consists of the N-terminal (N) and first kringle (K) domain and requires heparan sulfate or solub

238 hat consists of the N terminal (N) and first kringle (K) domains and retains receptor binding and sig

239 o(a) size isoform containing either 14 or 17 kringle (K) IVs were isolated from the plasma of healthy

240 hat consists of the N-terminal (N) and first kringle (K1) domains and has partial agonistic activity.

241 hat consists of the N-terminal (N) and first kringle (K1) domains of full-length HGF and stimulates a

242 tain the N-terminal domain (N) and the first kringle (K1) or the first two kringle domains of HGF.

243 arboxyglutamate domain (Gla) followed by two kringles (K1 and K2).

244 asminogen fragments containing three or five kringles (K1-3 or K1-5) have an anti-angiogenic effect,

245 Angiostatin, the N-terminal four kringles (K1-4) of plasminogen, blocks tumor-mediated an

246 mmunoglobulin (Ig), cysteine-rich (CRD), and kringle (Kri) domains.

247 was lost when WT-sc-uPA was replaced with a kringle-less mutant (DeltaK-sc-uPA), which does not bind

248 kringles, thus interfering with a requisite kringle-ligand hydrophobic interaction.

249 K.Pm catalytic complex and its regulation by kringle ligands.

250 Our data show that the Kringle-like domain facilitates the resolution of disulf

251 esidues within the non-amyloid cysteine-rich Kringle-like domain stabilizes the disulfide-bonded dime

252 st that different conformations of the inter-kringle linker domain determine the functional behavior

253 inal Gla domain to kringle-1 (Lnk1), the two kringles (Lnk2), and kringle-2 to the C-terminal proteas

254 have found that AMCHA binds at the canonical kringle lysine binding site (LBS), structured by the Pro

255 All three kringle lysine-binding sites contain a bound bicine mole

256 g that an unoccupied Lys-binding site of the kringles may be required for integrin binding.

257 ts suggest that plasmin induces migration by kringle-mediated binding to alpha(9)beta(1) and simultan

258 forms containing one kringle (mini-Pg) or no kringles (micro-Pg).

259 gle domains, than in Pg forms containing one kringle (mini-Pg) or no kringles (micro-Pg).

260 r protein that functionally interacts with a kringle module, and serves as a paradigm for this import

261 re increased substantially when bound to the kringle module, in agreement with the X-ray results.This

262 aggregation occurred in the apo form of the kringle module.

263 EK-30/K2(Pg) dynamics results from different kringle modules complexed with small lysine analogs.

264 The kringle modules of apolipoprotein(a) [apo(a)] of lipopro

265 as the linker mutants Y124A or N127A or the kringle mutant V140A:I142A, bind the MET receptor with a

266 D antibody, whereas neither the isolated uPA kringle nor serine protease domain supported adhesion di

267 , we demonstrate for the first time that the kringles of angiostatin play different roles in inhibiti

268 lysine-binding site (LBS) interactions with kringles on Pg and Pm, as evidenced by inhibition of the

269 used to determine that the first of the two kringles plays a more important role in the recognition

270 e lysine-binding sites on the amino-terminal kringle portion of the plasminogen molecule play a role

271 Together the three kringles produce a central cavity suggestive of a unique

272 ermore, as observed in PMCA, plasminogen and kringles promoted PrP(Sc) propagation in ScN2a and Elk 2

273 neuroblastoma (ScN2a) cells and identified a kringle protein domain using full-length recombinant mou

274 lding of rNK1/K1 when in the presence of the kringle-specific ligand AMCHA, which left the rNK1/N T(m

275 ed via intrinsic fluorescence titration with kringle-specific omega-aminocarboxylic acid ligands.

276 of angiostatin kringles 1-3, the first multi-kringle structure to be determined.

277 Prothrombin contains two kringle structures, and expression of additional rFII/hF

278 flexibility of the linker connecting the two kringles suggests multiple arrangements for kringle-1 re

279 d extended into solvent perpendicular to the kringle surface, leaving the hydrophobic pocket and the

280 cing the key aromatic residue found in other kringles, thus interfering with a requisite kringle-liga

281 LBS and are not conserved among the other Pg kringles, thus providing a molecular basis for the selec

282 d in the conversion of a weak ligand binding kringle to one that possesses an affinity for omega-amin

283 size of the major apo(a) isoform (number of kringle type IV repeats) was negatively associated with

284 erminal domain of apo(a) containing 6 type-4 kringles (types 5 to 10), kringle V, and the protease do

285 We have previously shown that kringle V (KV) is the site of oxPL linkage in human apo(

286 that all or some of the six lysines in human kringle V are involved in Schiff base linkage with oxPtd

287 containing apo(a) fragment, rIII, containing kringle V but not the protease domain.

288 inding that apo(a) of rhesus monkeys lacking kringle V did not react with EO6.

289 onsists of 10 kringle IV domains (KIVs), one kringle V domain, and an inactive protease domain.

290 A monoclonal antibody specific for Kringle V inhibited the apo(a)-mediated effect on IL-8.

291 The evidence that kringle V is critical for EO6 reactivity is supported by

292 udies provide evidence that in human apo(a), kringle V is the site that reacts with EO6 via lysine-ox

293 aminin alpha2, endostatin, endorepellin, and kringle V), can modulate autophagic signaling pathways.

294 ontaining 6 type-4 kringles (types 5 to 10), kringle V, and the protease domain was demonstrated to c

295 y the enzymatic digestion of apo(a) and also kringle V-containing apo(a) recombinants.

296 inal domain, F2 (but not the N-terminal F1), kringle V-containing fragments obtained by the enzymatic

297 apo(a), an activity mostly contained in the Kringle V-protease region.

298 , is assisted by SK Lys(414) binding to a Pm kringle, which accounts for a 11-20-fold affinity decrea

299 interaction of the lysine-binding site of a kringle with an internal pseudo-lysine residue of a pept

300 locking of lysine-binding sites (LBSs) on Pg kringles with 6-aminohexanoic acid or benzamidine.

301 The differences in dynamics observed for kringles with different ligands provide what we believe