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1pmk

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Revision as of 06:52, 29 November 2017

KRINGLE-KRINGLE INTERACTIONS IN MULTIMER KRINGLE STRUCTURES

Structural highlights

1pmk is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Activity:	Plasmin, with EC number 3.4.21.7
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[PLMN_HUMAN] Defects in PLG are the cause of plasminogen deficiency (PLGD) [MIM:217090]. PLGD is characterized by decreased serum plasminogen activity. Two forms of the disorder are distinguished: type 1 deficiency is additionally characterized by decreased plasminogen antigen levels and clinical symptoms, whereas type 2 deficiency, also known as dysplasminogenemia, is characterized by normal, or slightly reduced antigen levels, and absence of clinical manifestations. Plasminogen deficiency type 1 results in markedly impaired extracellular fibrinolysis and chronic mucosal pseudomembranous lesions due to subepithelial fibrin deposition and inflammation. The most common clinical manifestation of type 1 deficiency is ligneous conjunctivitis in which pseudomembranes formation on the palpebral surfaces of the eye progresses to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

Function

[PLMN_HUMAN] Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells.^[9] Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo.^[10]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The crystal structure of a monoclinic form of human plasminogen kringle 4 (PGK4) has been solved by molecular replacement using the orthorthombic structure as a model and it has been refined by restrained least-squares methods to an R factor of 16.4% at 2.25 A resolution. The X-PLOR structure of kringle 2 of tissue plasminogen activator (t-PAK2) has been refined further using PROFFT (R = 14.5% at 2.38 A resolution). The PGK4 structure has 2 and t-PAK2 has 3 independent molecules in the asymmetric unit. There are 5 different noncrystallographic symmetry "dimers" in PGK4. Three make extensive kringle-kringle interactions related by noncrystallographic 2(1) screw axes without blocking the lysine binding site. Such associations may occur in multikringle structures such as prothrombin, hepatocyte growth factor, plasminogen (PG), and apolipoprotein [a]. The t-PAK2 structure also has noncrystallographic screw symmetry (3(1)) and mimics fibrin binding mode by having lysine of one molecule interacting electrostatically with the lysine binding site of another kringle. This ligand-like binding interaction may be important in kringle-kringle interactions involving non-lysine binding kringles with lysine or pseudo-lysine binding sites. Electrostatic intermolecular interactions involving the lysine binding site are also found in the crystal structures of PGK1 and orthorhombic PGK4. Anions associate with the cationic centers of these and t-PAK2 that appear to be more than occasional components of lysine binding site regions.

Kringle-kringle interactions in multimer kringle structures.,Padmanabhan K, Wu TP, Ravichandran KG, Tulinsky A Protein Sci. 1994 Jun;3(6):898-910. PMID:8069221^[11]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ichinose A, Espling ES, Takamatsu J, Saito H, Shinmyozu K, Maruyama I, Petersen TE, Davie EW. Two types of abnormal genes for plasminogen in families with a predisposition for thrombosis. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):115-9. PMID:1986355
↑ Azuma H, Uno Y, Shigekiyo T, Saito S. Congenital plasminogen deficiency caused by a Ser572 to Pro mutation. Blood. 1993 Jul 15;82(2):475-80. PMID:8392398
↑ Miyata T, Iwanaga S, Sakata Y, Aoki N. Plasminogen Tochigi: inactive plasmin resulting from replacement of alanine-600 by threonine in the active site. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6132-6. PMID:6216475
↑ Miyata T, Iwanaga S, Sakata Y, Aoki N, Takamatsu J, Kamiya T. Plasminogens Tochigi II and Nagoya: two additional molecular defects with Ala-600----Thr replacement found in plasmin light chain variants. J Biochem. 1984 Aug;96(2):277-87. PMID:6238949
↑ Kikuchi S, Yamanouchi Y, Li L, Kobayashi K, Ijima H, Miyazaki R, Tsuchiya S, Hamaguchi H. Plasminogen with type-I mutation is polymorphic in the Japanese population. Hum Genet. 1992 Sep-Oct;90(1-2):7-11. PMID:1427790
↑ Schuster V, Mingers AM, Seidenspinner S, Nussgens Z, Pukrop T, Kreth HW. Homozygous mutations in the plasminogen gene of two unrelated girls with ligneous conjunctivitis. Blood. 1997 Aug 1;90(3):958-66. PMID:9242524
↑ Higuchi Y, Furihata K, Ueno I, Ishikawa S, Okumura N, Tozuka M, Sakurai N. Plasminogen Kanagawa-I, a novel missense mutation, is caused by the amino acid substitution G732R. Br J Haematol. 1998 Dec;103(3):867-70. PMID:9858247
↑ Schuster V, Seidenspinner S, Zeitler P, Escher C, Pleyer U, Bernauer W, Stiehm ER, Isenberg S, Seregard S, Olsson T, Mingers AM, Schambeck C, Kreth HW. Compound-heterozygous mutations in the plasminogen gene predispose to the development of ligneous conjunctivitis. Blood. 1999 May 15;93(10):3457-66. PMID:10233898
↑ Rossignol P, Ho-Tin-Noe B, Vranckx R, Bouton MC, Meilhac O, Lijnen HR, Guillin MC, Michel JB, Angles-Cano E. Protease nexin-1 inhibits plasminogen activation-induced apoptosis of adherent cells. J Biol Chem. 2004 Mar 12;279(11):10346-56. Epub 2003 Dec 29. PMID:14699093 doi:10.1074/jbc.M310964200
↑ Rossignol P, Ho-Tin-Noe B, Vranckx R, Bouton MC, Meilhac O, Lijnen HR, Guillin MC, Michel JB, Angles-Cano E. Protease nexin-1 inhibits plasminogen activation-induced apoptosis of adherent cells. J Biol Chem. 2004 Mar 12;279(11):10346-56. Epub 2003 Dec 29. PMID:14699093 doi:10.1074/jbc.M310964200
↑ Padmanabhan K, Wu TP, Ravichandran KG, Tulinsky A. Kringle-kringle interactions in multimer kringle structures. Protein Sci. 1994 Jun;3(6):898-910. PMID:8069221

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1pmk"

Categories: Human | Plasmin | Padmanabhan, K | Tulinsky, A

@@ Line 1: / Line 1: @@
 ==KRINGLE-KRINGLE INTERACTIONS IN MULTIMER KRINGLE STRUCTURES==
 <StructureSection load='1pmk' size='340' side='right' caption='[[1pmk]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[1pmk]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PMK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1PMK FirstGlance]. <br>
 </td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Plasmin Plasmin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.7 3.4.21.7] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pmk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pmk OCA], [http://pdbe.org/1pmk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1pmk RCSB], [http://www.ebi.ac.uk/pdbsum/1pmk PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pmk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pmk OCA], [http://pdbe.org/1pmk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1pmk RCSB], [http://www.ebi.ac.uk/pdbsum/1pmk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1pmk ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 29: / Line 30: @@
 </div>
 <div class="pdbe-citations 1pmk" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Plasminogen|Plasminogen]]
 == References ==
 <references/>

1pmk

From Proteopedia

Revision as of 06:52, 29 November 2017

KRINGLE-KRINGLE INTERACTIONS IN MULTIMER KRINGLE STRUCTURES

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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