1a5i: Difference between revisions
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==Overview== | ==Overview== | ||
The saliva of the blood-eating vampire bat Desmodus rotundus contains, plasminogen activators (PAs) that maintain the fluidity of the prey's, blood by activating plasminogen and dissolving developing fibrin clots. D., rotundus salivary PAs (DSPAs) are composed of evolutionarily conserved, domains reminiscent of human tissue-type PA (tPA), but their catalytic, domain lacks a plasmin-sensitive "activation cleavage site". Despite this, all DSPAs are intrinsically active and enormously stimulated in the, presence of fibrin. The recombinant catalytic domain of DSPAalpha1 has, been crystallized in a covalent complex with Glu-Gly-Arg-chloromethyl, ketone and its structure solved at 2.9 A resolution. The structure is, similar to that of activated two-chain human tPA. Despite its single-chain, ... | The saliva of the blood-eating vampire bat Desmodus rotundus contains, plasminogen activators (PAs) that maintain the fluidity of the prey's, blood by activating plasminogen and dissolving developing fibrin clots. D., rotundus salivary PAs (DSPAs) are composed of evolutionarily conserved, domains reminiscent of human tissue-type PA (tPA), but their catalytic, domain lacks a plasmin-sensitive "activation cleavage site". Despite this, all DSPAs are intrinsically active and enormously stimulated in the, presence of fibrin. The recombinant catalytic domain of DSPAalpha1 has, been crystallized in a covalent complex with Glu-Gly-Arg-chloromethyl, ketone and its structure solved at 2.9 A resolution. The structure is, similar to that of activated two-chain human tPA. Despite its single-chain, status, the activation domain is observed in an enzymatically active, conformation, with a functional substrate binding site and active site, accommodating the peptidylmethylene inhibitor. The activation pocket, which normally receives the N-terminal Ile16, is occupied by the side, chain of Lys156, whose distal ammonium group makes an internal salt bridge, with the carboxylate group of Asp194. Lys156 is in a groove shielded from, the bulk solvent by the intact "activation loop" (Gln10-Phe21), favoring, Lys156-Asp194 salt bridge formation and stabilization of a functional, substrate binding site. Together with the characteristic 186 insertion, loop, the activation loop could act as a switch, effecting full, single-chain enzymatic activity upon binding to fibrin. | ||
==About this Structure== | ==About this Structure== | ||
1A5I is a | 1A5I is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Desmodus_rotundus Desmodus rotundus] with CH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/T-plasminogen_activator T-plasminogen activator], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.68 3.4.21.68] Structure known Active Site: NUL. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1A5I OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: serine protease]] | [[Category: serine protease]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:37:57 2007'' | ||
Revision as of 15:32, 5 November 2007
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CATALYTIC DOMAIN OF VAMPIRE BAT (DESMODUS ROTUNDUS) SALIVA PLASMINOGEN ACTIVATOR IN COMPLEX WITH EGR-CMK (GLU-GLY-ARG CHLOROMETHYL KETONE)
OverviewOverview
The saliva of the blood-eating vampire bat Desmodus rotundus contains, plasminogen activators (PAs) that maintain the fluidity of the prey's, blood by activating plasminogen and dissolving developing fibrin clots. D., rotundus salivary PAs (DSPAs) are composed of evolutionarily conserved, domains reminiscent of human tissue-type PA (tPA), but their catalytic, domain lacks a plasmin-sensitive "activation cleavage site". Despite this, all DSPAs are intrinsically active and enormously stimulated in the, presence of fibrin. The recombinant catalytic domain of DSPAalpha1 has, been crystallized in a covalent complex with Glu-Gly-Arg-chloromethyl, ketone and its structure solved at 2.9 A resolution. The structure is, similar to that of activated two-chain human tPA. Despite its single-chain, status, the activation domain is observed in an enzymatically active, conformation, with a functional substrate binding site and active site, accommodating the peptidylmethylene inhibitor. The activation pocket, which normally receives the N-terminal Ile16, is occupied by the side, chain of Lys156, whose distal ammonium group makes an internal salt bridge, with the carboxylate group of Asp194. Lys156 is in a groove shielded from, the bulk solvent by the intact "activation loop" (Gln10-Phe21), favoring, Lys156-Asp194 salt bridge formation and stabilization of a functional, substrate binding site. Together with the characteristic 186 insertion, loop, the activation loop could act as a switch, effecting full, single-chain enzymatic activity upon binding to fibrin.
About this StructureAbout this Structure
1A5I is a Single protein structure of sequence from Desmodus rotundus with CH2 as ligand. Active as T-plasminogen activator, with EC number 3.4.21.68 Structure known Active Site: NUL. Full crystallographic information is available from OCA.
ReferenceReference
Catalytic domain structure of vampire bat plasminogen activator: a molecular paradigm for proteolysis without activation cleavage., Renatus M, Stubbs MT, Huber R, Bringmann P, Donner P, Schleuning WD, Bode W, Biochemistry. 1997 Nov 4;36(44):13483-93. PMID:9354616
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