1l4d: Difference between revisions
New page: left|200px<br /> <applet load="1l4d" size="450" color="white" frame="true" align="right" spinBox="true" caption="1l4d, resolution 2.3Å" /> '''CRYSTAL STRUCTURE OF... |
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[[Image:1l4d.gif|left|200px]]<br /> | [[Image:1l4d.gif|left|200px]]<br /><applet load="1l4d" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1l4d, resolution 2.3Å" /> | caption="1l4d, resolution 2.3Å" /> | ||
'''CRYSTAL STRUCTURE OF MICROPLASMINOGEN-STREPTOKINASE ALPHA DOMAIN COMPLEX'''<br /> | '''CRYSTAL STRUCTURE OF MICROPLASMINOGEN-STREPTOKINASE ALPHA DOMAIN COMPLEX'''<br /> | ||
==Overview== | ==Overview== | ||
Streptokinase (SK) is a thrombolytic agent widely used for the clinical | Streptokinase (SK) is a thrombolytic agent widely used for the clinical treatment of clotting disorders such as heart attack. The treatment is based on the ability of SK to bind plasminogen (Pg) or plasmin (Pm), forming complexes that proteolytically activate other Pg molecules to Pm, which carries out fibrinolysis. SK contains three major domains. The N-terminal domain, SKalpha, provides the complex with substrate recognition towards Pg. SKalpha contains a unique mobile loop, residues 45-70, absent in the corresponding domains of other bacterial Pg activators. To study the roles of this loop, we deleted 12 residues in this loop in both full-length SK and the SKalpha fragment. Kinetic data indicate that this loop participates in the recognition of substrate Pg, but does not function in the active site formation in the activator complex. Two crystal structures of the deletion mutant of SKalpha (SKalpha(delta)) complexed with the protease domain of Pg were determined. While the structure of SKalpha(delta) is essentially the same as this domain in full-length SK, the mode of SK-Pg interaction was however different from a previously observed structure. Even though mutagenesis studies indicated that the current complex represents a minor interacting form in solution, the binding to SKalpha(delta) triggered similar conformational changes in the Pg active site in both crystal forms. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1L4D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Streptococcus_dysgalactiae_subsp._equisimilis Streptococcus dysgalactiae subsp. equisimilis] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | 1L4D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Streptococcus_dysgalactiae_subsp._equisimilis Streptococcus dysgalactiae subsp. equisimilis] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L4D OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Streptococcus dysgalactiae subsp. equisimilis]] | [[Category: Streptococcus dysgalactiae subsp. equisimilis]] | ||
[[Category: Loy, J | [[Category: Loy, J A.]] | ||
[[Category: Tang, J.]] | [[Category: Tang, J.]] | ||
[[Category: Terzyan, S.]] | [[Category: Terzyan, S.]] | ||
[[Category: Wakeham, N.]] | [[Category: Wakeham, N.]] | ||
[[Category: Zhai, P.]] | [[Category: Zhai, P.]] | ||
[[Category: Zhang, X | [[Category: Zhang, X C.]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
[[Category: crystal structure]] | [[Category: crystal structure]] | ||
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[[Category: streptokinase]] | [[Category: streptokinase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:41:12 2008'' | ||
Revision as of 14:41, 21 February 2008
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CRYSTAL STRUCTURE OF MICROPLASMINOGEN-STREPTOKINASE ALPHA DOMAIN COMPLEX
OverviewOverview
Streptokinase (SK) is a thrombolytic agent widely used for the clinical treatment of clotting disorders such as heart attack. The treatment is based on the ability of SK to bind plasminogen (Pg) or plasmin (Pm), forming complexes that proteolytically activate other Pg molecules to Pm, which carries out fibrinolysis. SK contains three major domains. The N-terminal domain, SKalpha, provides the complex with substrate recognition towards Pg. SKalpha contains a unique mobile loop, residues 45-70, absent in the corresponding domains of other bacterial Pg activators. To study the roles of this loop, we deleted 12 residues in this loop in both full-length SK and the SKalpha fragment. Kinetic data indicate that this loop participates in the recognition of substrate Pg, but does not function in the active site formation in the activator complex. Two crystal structures of the deletion mutant of SKalpha (SKalpha(delta)) complexed with the protease domain of Pg were determined. While the structure of SKalpha(delta) is essentially the same as this domain in full-length SK, the mode of SK-Pg interaction was however different from a previously observed structure. Even though mutagenesis studies indicated that the current complex represents a minor interacting form in solution, the binding to SKalpha(delta) triggered similar conformational changes in the Pg active site in both crystal forms.
DiseaseDisease
Known diseases associated with this structure: Conjunctivitis, ligneous OMIM:[173350], Plasminogen Tochigi disease OMIM:[173350], Plasminogen deficiency, types I and II OMIM:[173350], Thrombophilia, dysplasminogenemic OMIM:[173350]
About this StructureAbout this Structure
1L4D is a Protein complex structure of sequences from Homo sapiens and Streptococcus dysgalactiae subsp. equisimilis with as ligand. Active as Plasmin, with EC number 3.4.21.7 Full crystallographic information is available from OCA.
ReferenceReference
Effects of deletion of streptokinase residues 48-59 on plasminogen activation., Wakeham N, Terzyan S, Zhai P, Loy JA, Tang J, Zhang XC, Protein Eng. 2002 Sep;15(9):753-61. PMID:12456874
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