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

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

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

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

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

10 In contrast, kringle 1-3, which is equivalent to angiostatin in inhib

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

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

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

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

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

16 through a high-affinity interaction between kringles 1 through 3 of plasminogen and the extracellula

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

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

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

20 und an additional interaction between HK and kringles 1-3 enhancing the inhibitory effect, presumably

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 Plg cleavage by HNE (PlgHNE) yielded kringles 1-3, kringle 4 and mini-plasminogen.

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

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

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

31 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 structure of the amino-terminal domain or in kringle 2 have been replaced.

53 1 is removed from kringle 1-3, the resulting kringle 2-3 becomes more potent than kringle 1-3.

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

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

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

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

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

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

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 eavage by HNE (PlgHNE) yielded kringles 1-3, kringle 4 and mini-plasminogen.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

97 2; a nonlinear epitope contained within the kringle 5 domain and the latent protease domain; and a n

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

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

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

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

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

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

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

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

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

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

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

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

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

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

112 tion is likely due to complex formation with kringle 5 without interfering with plasmin's active site

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

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

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

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

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

118 beta domain additionally interacts with Plg kringle 5.

119 ional lysine binding site within plasminogen kringle 5.

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

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

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

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

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

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

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

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

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

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

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 giostatin, demonstrating the significance of kringle conformation in maintaining the anti-angiogenic

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

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

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

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

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

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

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

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

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 meric cDNAs with the propeptide/Gla domains, kringle domain, and serine protease domain exchanged bet

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

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

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 omposed of only the amino terminus and first kringle domain.

164 in nucleolin through a region containing the kringle domain.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

181 ary aim of our study was to characterize the kringle domains of angiostatin for their inhibitory acti

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

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

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

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

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

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

194 of four homologous triple-disulfide bridged kringle domains, has previously been shown to exhibit pr

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

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

197 ormation of Pg through interactions with the kringle domains.

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

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

200 ructural makeup from a composite of multiple kringle domains.

201 pecific for plasminogen and conserved in its kringle domains.

202 scope of potential biological functions for kringle domains.

203 3:2 ratio, with the distance between the two kringles either fully extended (54 +/- 2 A) or partially

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

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

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

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

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

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

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

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

212 1 domain of factor XI, we conclude that the Kringle II domain of prothrombin competes with HK for bi

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

229 19 bond located in the linker region between kringles IV-4 and IV-5, a bond immediately upstream of t

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

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

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

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

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

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

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

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

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

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

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

241 by the companion much stronger affinity HPg kringles, K1HPg and K4HPg.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

266 he basic amino acid, arginine, that in other kringle polypeptides forms the donor cationic center for

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

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

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

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

271 binding of omega-amino acids to this mutant kringle (r-K5HPg[L71R]) was restored to levels displayed

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

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

274 We also show that disruption of the kringle structure by reducing/alkylating agents markedly

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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