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Topic: Kringle domain

	Direct interaction of the kringle domain of urokinase-type plasminogen activator (uPA) and integrin alpha v beta 3 ...
		The isolated uPA kringle domain binds specifically to purified, recombinant soluble, and cell surface alpha v beta 3, and other integrins (alpha 4 beta 1 and alpha 9 beta 1), and induced migration of CHO cells in an alpha v beta 3-dependent manner.
		The binding of the uPA kringle to alpha v beta 3 and uPA kringle-induced alpha v beta 3-dependent cell migration were blocked by homologous plasminogen kringles 1-3 or 1-4 (angiostatin), a known integrin antagonist.
		Endothelial cells bound to and migrated on uPA and uPA kringle in an alpha v beta 3-dependent manner.
	repositories.cdlib.org /postprints/1940 (464 words)

	Directed evolution of proteins by exon shuffling - Nature Biotechnology (Site not responding. Last check: 2007-10-16)
		The observation that these domains are also found in otherwise unrelated proteins like apolipoprotein A (kringle domains), fibronectin (fibronectin type I and type II domains), and low-density lipoprotein receptor (EGF-like domains) opens the possibility that the noncatalytic regions of the hemostatic proteases were assembled from individual domains by exon shuffling.
		Removal of the two N-terminal domains increased the plasma half-life of this enzyme, while the affinity for plasmin-digested fibrin was maintained by insertion of the kringle 1 domain of plasminogen.
		Tordai, H., Banyai, L. and Patthy, L. The PAN module: the N-terminal domains of plasminogen and hepatocyte growth factor are homologous with the apple domains of the prekallikrein family and with a novel domain found in numerous nematode proteins.
	www.nature.com /cgi-taf/DynaPage.taf?file=/nbt/journal/v19/n5/full/nbt0501_423.html (4261 words)

	Thrombus formation on a fissured or disrupted atherosclerotic plaque is the main pathogenetic mechanism for the acute ...
		A fibronectin "finger" domain (contributes to fibrin binding), two "kringle" domains (also bind to fibrin), and an epidermal growth factor domain are also present.
		Kringles are triple-looped, disulfide cross-linked domains found in a varying number of copies, in some serine proteases and plasma proteins.
		Kringle domains are thought to play a role in binding mediators, such as membranes, other proteins or phospholipids, and in the regulation of proteolytic activity.
	www.usc.edu /hsc/pharmacy/curriculum/l3/phar546/tPAThrombolysis.htm (2425 words)

	Patent 6,576,610
		Kringle domains, which are present in several proteins, contain about eighty amino acids that are rigidly constrained by six highly conserved cysteine residues that form three disulfides in an intertwined 1-6, 2-4, and 3-5 pattern.
		The kringle domains in plasminogen bind other plasma proteins, cells, cell-associated proteins, and fibrin clots, and such binding appears to depend on specific lysine residues in the kringle domain.
		Kringle 5, which is not part of angiostatin, also inhibits endothelial cell growth, and is a selective inhibitor for endothelial cell migration (IC50=500 nM).
	www.pharmcast.com /Patents/Yr2003/Jun2003/061003/6576610_Context061003.htm (7453 words)

	PPS '97 - Tertiary Structure: Mosaic Proteins
		Domains in such a protein may be considered to be connected units which are independent in terms of their structure, function and folding behaviour.
		This 94-residue domain is of the immunoglobulin beta-sandwich type, consisting of 7 strands forming two sheets in "Greek-key" arrangement (see section on all-beta protein folds).
		On each of the 4 chains, the N-terminal domains are known as variable domains, as the loops connecting the beta strands are subject to exon shuffling, creating the diversity of antibodies capable of binding to a variety of antigens.
	www.med.unibs.it /~marchesi/pps97/course/section10/mosaic.html (1367 words)

	Structural features of the kringle domain determine the intracellular degradation of under-gamma -carboxylated ... (Site not responding. Last check: 2007-10-16)
		The kringle domain therefore is critical in determining the metabolic
		There are two separate kringle structures in the kringle domain of prothrombin.
		of the kringle domain in the intracellular processing/degradation
	www.pnas.org /cgi/content/full/94/25/13654 (3437 words)

	Cyclopeptides - 25 Or More Peptide Repeating Units In Known Peptide Chain Structure patents
		The present invention concerns fusion of Fc domains with biologically active peptides and a process for preparing pharmaceutical agents using biologically active peptides.
		In some embodiments, the protein transduction domain comprises the protein transduction domain of...
		The present invention is directed to fusion peptides comprising a fungal targeting agent and a channel-forming domain consisting essentially of amino acids 451-626 of colicin Ia, as well as the polynucleotides encoding the peptides of the invention.
	www.freshpatents.com /x1514012000psbc.php (12741 words)

	Identification of Two Functionally Distinct Lysine-binding Sites in Kringle 37 and in Kringles 32-36 of Human ...
		LBS I is situated in kringle 37 of apo(a) and is responsible for the 30.6% lysine binding of wild type r-Lp(a) particles observed in the absence of Tween.
		Crystals of tissue plasminogen activator kringle 2 represent an example where the lysine-binding pocket of one kringle is occupied by an internal lysine from another kringle(58).
		Additionally or alternatively to lysine binding, other noncovalent interactions between the deleted domain(s) and LDL might be involved in Lp(a) complex formation although the dose-dependent inhibition by EACA of the in vitro association between transgenic apo(a) and human LDL (14) argues in favor of a role of lysine binding during Lp(a) assembly.
	www.jbc.org /cgi/content/full/270/11/6227 (7086 words)

	TERTIARY STRUCTURE- MOSAIC PROTEINS
		This 94-residue domain is of the immunoglobulin beta-sandwich type, consisting of 7 strands forming two sheets in "Greek-key" arrangement (see future chapter on protein folds).
		The kringle fold is rich in disulphide bonds (three are visible in the NMR structure) and is composed mostly of beta strands but there is one helix.
		This same tPA kringle domain has also been crystallized and the structure can be seen here (there are 3 kringle domains in the asymmetric unit).
	www.cryst.bbk.ac.uk /PPS95/course/7_tertiary/mosaic.html (1217 words)

	Sample Answer for homework 1: (Site not responding. Last check: 2007-10-16)
		Homology domain is a domain found in a homology domain superfamily.
		The Kringle domain runs from 70 to about 150, and the trypsin-like serine protease domain runs from 178 to 419.
		Domains clustered in the same sequence families have sequence identities >35% (with at least 60% of the larger domain equivalent to the smaller), indicating highly similar structures and functions.
	www.sdsc.edu /~wilfred/genomes/lectures/homework1_answer.htm (1744 words)

	Ligand interactions with the kringle 5 domain of plasminogen. A study by 1H NMR spectroscopy.
		A study by 1H NMR spectroscopy.The binding of small molecules to the kringle 5 domain fragment of human plasminogen has been investigated by 1H NMR spectroscopy at 300 MHz.
		The higher affinities toward both benzylamine and epsilon ACA indicate that a free carboxylate group is not, by itself, a main determinant of ligand-binding to kringle 5.
		It is suggested that, although weak (0.1 approximately less than Ka approximately less than 0.6 mM-1), these interactions could be of physiological relevance in the context of plasminogen binding to the fibrin clot.
	www.pdg.cnb.uam.es /UniPub/iHOP/gp/5323.html (312 words)

	Convergent evolution of apolipoprotein(a) in primates and hedgehog -- Lawn et al. 94 (22): 11992 -- Proceedings of ... (Site not responding. Last check: 2007-10-16)
		domain, and a proteolytically inactive relative of the protease
		kringle 4 domains of plasminogen and apo(a) diverged at a constant
		Relationship of the kringle 4 domains of plasminogen and primate apo(a).
	www.pnas.org /cgi/content/full/94/22/11992 (4416 words)

	NCBI CDD pfam00051
		Kringle domains have been found in plasminogen, hepatocyte growth factors, prothrombin, and apolipoprotein A. Structure is disulfide-rich, nearly all-beta.
		These domain models are grouped with pfam00051 because some sequences that hit these models using RPS-BLAST also hit pfam00051 in an overlapping interval, with significant E-values.
		(2007), "CDD: a conserved domain database for interactive domain family analysis.
	www.ncbi.nlm.nih.gov /Structure/cdd/cddsrv.cgi?uid=pfam00051 (114 words)

	The kringle stabilizes urokinase binding to the urokinase receptor -- Bdeir et al. 102 (10): 3600 -- Blood (Site not responding. Last check: 2007-10-16)
		The kringle stabilizes urokinase binding to the urokinase receptor
		a receptor-binding epitope is not exposed in the isolated kringle
		Of note is the variability in the spatial relationship between the GFD and kringle domains.
	www.bloodjournal.org /cgi/content/full/102/10/3600 (6512 words)

	Antiangiogenic Activity of a Domain Deletion Mutant of Tissue Plasminogen Activator Containing Kringle 2 -- Carroll et ...
		by the presence of the kringle 2 domain.
		uPA, and with the kringle 1 domain of tPA.
		Inhibition of endothelial cell proliferation by the recombinant kringle domain of tissue-type plasminogen activator.
	atvb.ahajournals.org /cgi/content/full/25/4/736 (3772 words)

	Characterization of kringle domains of angiostatin as antagonists of endothelial cell migration, an important process ... (Site not responding. Last check: 2007-10-16)
		Characterization of kringle domains of angiostatin as antagonists of endothelial cell migration, an important process in angiogenesis -- Ji et al.
		The human plasminogen molecule is composed of a signal sequence, a preactivation domain, 5 triple-disulfide bridged kringle structures, and a protease domain.
		Kringle structures are essential for the anti-migratory activities of angiostatin.
	www.fasebj.org /cgi/content/full/12/15/1731 (4763 words)

	Tissue Plasminogen Activator (Site not responding. Last check: 2007-10-16)
		are contained within the heavy A chain and is mediated the finger domain via the second kringle region.
		The structures involved in the enzymatic domain are in the B chain.
		The plasmin that is formed on the surface of fibrin within the clot has both of its lysine binding sites occupied and is protected therefore from rapid inactivation by alpha-2 antiplasmin (t 1/2 is about 10 to 100 seconds).
	www.umich.edu /~pharm660/AnticoagAntiplat/tsld085.htm (143 words)

	[No title]
		A series of intragenic duplications of the kringle domain, gene duplications, exon shuffling and deletions is responsible for the genes currently present in mammals, avians and amphibians.
		Important among the ligands of the kringles are positive activation effectors, typified by lysine and its analogues, and negative activation effectors, such as Cl—.
		MSP causes phosphorylation of the receptor cytoplasmic domain, association of phosphatidylinositol (PI)-3 kinase with the receptor, and phosphorylation of receptor-bound PI-3 kinase.
	www.novartisfound.org.uk /catalog/212abs.htm (2703 words)

	The Llinás group - Research - Urokinase Plasminogen Activator Kringle Domain
		The solution structure of the kringle domain from urokinase-type plasminogen activator (u-PA) has been determined using 1H nuclear magnetic resonance spectroscopy and dynamical simulated annealing calculations.
		A total of 35 structures, 20 generated using a distance geometry method prior to simulated annealing and 15 generated using initial random phi, psi values, have been calculated based on 946 experimental nuclear Overhauser effect distance constraints and 48 dihedral angle constraints.
		Comparison between the u-PA kringle structure and the crystal and NMR solution structures of tissue-type plasminogen activator kringle 2 has shown that the two proteins have similar global folds but demonstrate a number of local differences.
	www.chem.cmu.edu /groups/Llinas/res/structure/upa.html (148 words)

	GeneCard for PLAT (Site not responding. Last check: 2007-10-16)
		Domain: Both FN1 and one of the kringle domains are required for binding to fibrin.
		Domain: The second kringle domain is implicated in binding to cytokeratin 8 and to the endothelial
		The 2.3 A crystal structure of the catalytic domain of recombinant two-chain human tissue-type plasminogen activator.
	bioinfo.cnio.es /cgi-bin/genecards/carddisp?PLAT (932 words)

	TSRI - News and Publications
		Apoprotein(a) is highly homologous to plasminogen; it contains 10 disulfide-bonded kringle domains homologous to plasminogen kringle 4, 1 domain homologous to plasminogen kringle 5, and a protease-like domain (that cannot develop proteolytic activity).
		Using surface plasmon resonance, we found that the apoprotein(a) kringle 5 domain interacts directly with fibrinogen and with plasmin-treated fibrinogen.
		Our results suggest that apoprotein(a) kringle 5 may be involved in the interaction of the native lipoprotein(a) particle with fibrinogen.
	www.scripps.edu /news/sr/sr2002/cb26.html (734 words)

	Abstract number: P409 (Site not responding. Last check: 2007-10-16)
		uPA is composed of three domains, a proteolytic domain (PD), a kringle domain (KD), and a growth factor-like domain (GFD), which mediates interaction with uPAR.
		Using the recombinant both wild-type uPA (uPAwt) and urokinase with a deletion of growth factor-like domain (uPADGFD), we demonstrate further, that, despite of inability to bind uPAR, uPADGFD was able to induce migration of human smooth muscle cells (SMC) and HEK293 cells in uPAwt-similar fashion (EC50 2 nM).
		The chemotactic effect of uPADGFD was attributed to the kringle domain, since separate recombinant uPA-kringle domain stimulated cell migration, while recombinant uPA-protease domain was ineffective.
	www.schattauer.de /abstracts/absP409.html (332 words)

	Protein disorder prediction: Implications for structural proteomics
		One focus of structural genomics initiatives is to solve structures for novel domains and thereby increase the coverage of fold and structure space (Brenner, 2000).
		These are proteins or domains that, in their native state, are either completely disordered or contain large disordered regions.
		Structures such as the Kringle domain (PDB: 1KRN) are almost entirely without regular secondary structure in their native state but they still have tertiary structure wherein the basic building block is coils.
	dis.embl.de /html/paper.html (5137 words)

	High-resolution crystal structure of apolipoprotein(a) kringle IV type 7: Insights into ligand binding -- Ye et al. 10 ... (Site not responding. Last check: 2007-10-16)
		De Serrano, V.S. and Castellino, F.J. Specific anionic residues of the recombinant kringle 2 domain of tissue-type plasminogen activator that are responsible for stabilization of its interaction with omega-amino acid ligand.
		Gabel, B.R. and Koschinsky, M.L. Sequences within apolipoprotein(a) kringle IV types 6–8 bind directly to low-density lipoprotein and mediate noncovalent association of apolipoprotein(a) with apolipoprotein B-100.
		McCance, S.G., Mengart, N., and Castellino, F.J. Amino acid residues of the kringle-4 and kringle-5 domains of human plasminogen that stabilize their interaction with omega-amino acid ligands.
	www.proteinscience.org /cgi/content/full/10/6/1124 (3098 words)

	International Society for Fibrinolysis and Proteolysis
		Contains a growth factor domain, a kringle domain and a serine protease domain.
		Contains a finger domain, a growth factor domain, two kringle domains and a serine protease domain.
		DSPA alpha 1 and DSPA alpha 2 lack a kringle domain; DSPA beta lacks the finger domain and a kringle domain, while DSPA gamma lacks the finger domain, the growth factor domain and a kringle domain.
	www.fibrinolysis.org /NewFiles/Proteins.html (1874 words)

	Common Design \| The Design Matrix
		Four different domains are used to build the plasminogen activator: one fibronectin type III domain, one epidermal growth factor domain, one kringle domain and one serine protease domain [4].
		As a result, you often find the fibronectin domain in a variety of different proteins in all different branches of life (front-loaded?) mediating interactions between the protein and other molecules [6].
		The serine protease domain is the business end of the protein, as it is the enzymatic part that activates another protein.
	www.thedesignmatrix.com /content/?p=35 (2143 words)

	ibt - immunological & biochemical testsystems GmbH
		Extracellular domain of BAFF receptor, produced in E.Coli is a single, non-glycosylated polypeptide chain containing 63 amino acids fused with GST tag and having a molecular mass of 33600 Dalton.
		In the brain BDNF has a trophic action on retinal, cholinergic, and dopaminergic neurons, and in the peripheral nervous system it acts on both motor and sensory neurons.
		Some protein domains of BDNF are identical with those of NGF and another neurotrophic factor, designated NT-3 (neurotrophin-3).Polyclonal antibodies raised against murine NGF have been shown to cross-react with both NT-3 and BDNF.
	www.afsbio.de /Englisch/miscella.htm (1699 words)

	Horst Ibelgaufts'COPE: Cytokines Online Pathfinder Encyclopaedia (Site not responding. Last check: 2007-10-16)
		The purified angiogenic inhibitor inhibited the growth of bovine capillary endothelial cells and was non cytotoxic.
		This molecule was identified as a prothrombin kringle-2 domain (fragment-2).
		Prothrombin kringle-2 domain can be released from prothrombin by cleavage with factor Xa, which also yields bioactive thrombin.
	www.copewithcytokines.de /cope.cgi?7954 (113 words)

	Pfam 18.0 : Kringle (Site not responding. Last check: 2007-10-16)
		Kringles are autonomous structural domains, found throughout the blood clotting and fibrinolytic proteins.Kringle domains are believed to play a role in binding mediators (e.g., membranes, other proteins or phospholipids), and in the regulation of proteolytic activity MEDLINE:3886654, MEDLINE:6373375, MEDLINE:2157850.
		Kringle domains MEDLINE:3131537, MEDLINE:3891096, MEDLINE:1879523 are characterised by a triple loop, 3-disulphide bridge structure, whose conformation is defined by a number of hydrogen bonds and small pieces of anti-parallel
		They are found in a varying number of copies in some plasma proteins including prothrombin and urokinase-type plasminogen activator, which are serine proteases belonging to MEROPS peptidase family S1A.
	pfam.wustl.edu /cgi-bin/getdesc?name=Kringle (116 words)

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