1uma
From Proteopedia
(New page: 200px<br /> <applet load="1uma" size="450" color="white" frame="true" align="right" spinBox="true" caption="1uma, resolution 2.0Å" /> '''ALPHA-THROMBIN (HIRU...) |
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| - | [[Image:1uma.gif|left|200px]]<br /> | + | [[Image:1uma.gif|left|200px]]<br /><applet load="1uma" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1uma, resolution 2.0Å" /> | caption="1uma, resolution 2.0Å" /> | ||
'''ALPHA-THROMBIN (HIRUGEN) COMPLEXED WITH NA-(N,N-DIMETHYLCARBAMOYL)-ALPHA-AZALYSINE'''<br /> | '''ALPHA-THROMBIN (HIRUGEN) COMPLEXED WITH NA-(N,N-DIMETHYLCARBAMOYL)-ALPHA-AZALYSINE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Kinetics for the hydrolysis of the chromogenic active site titrant N | + | Kinetics for the hydrolysis of the chromogenic active site titrant N alpha-(N,N-dimethylcarbamoyl)-alpha-azalysine p-nitrophenyl ester (Dmc-azaLys-ONp) catalyzed by bovine beta-trypsin, bovine alpha-thrombin, human alpha-thrombin, human Lys77-plasmin, human urinary kallikrein, the M(r) 33,000 and M(r) 54,000 species of human urokinase, as well as by porcine pancreatic beta-kallikrein-A and B have been obtained between pH 6.0 and 8.0, at 21.0 degrees C. Moreover, the three dimensional structure of the human alpha-thrombin-(hirugen).Dmc-azaLys acyl.enzyme complex has been analyzed and refined by X-ray crystallography at 2.0 A resolution (R-factor = 0.168). As observed for bovine beta-trypsin, the acylating inhibitor molecule is covalently bound to the Ser195 catalytic residue, filling the human alpha-thrombin S1 primary specificity subsite with its lysyl side-group. However, the carbonyl group of the scissile human alpha-thrombin.Dmc-azaLys acyl bond does not occupy properly the oxyanion binding hole. At variance from the bovine beta-trypsin.Dmc-azaLys acyl.enzyme structure, a second, not covalently bound, inhibitor molecule, partly shielded by the 60-insertion loop of human alpha-thrombin, is contacting the enzyme "aryl-binding site". |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1UMA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG and IN2 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http:// | + | 1UMA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=IN2:'>IN2</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UMA OCA]. |
==Reference== | ==Reference== | ||
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[[Category: serine protease]] | [[Category: serine protease]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:26:07 2008'' |
Revision as of 13:26, 21 February 2008
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ALPHA-THROMBIN (HIRUGEN) COMPLEXED WITH NA-(N,N-DIMETHYLCARBAMOYL)-ALPHA-AZALYSINE
Contents |
Overview
Kinetics for the hydrolysis of the chromogenic active site titrant N alpha-(N,N-dimethylcarbamoyl)-alpha-azalysine p-nitrophenyl ester (Dmc-azaLys-ONp) catalyzed by bovine beta-trypsin, bovine alpha-thrombin, human alpha-thrombin, human Lys77-plasmin, human urinary kallikrein, the M(r) 33,000 and M(r) 54,000 species of human urokinase, as well as by porcine pancreatic beta-kallikrein-A and B have been obtained between pH 6.0 and 8.0, at 21.0 degrees C. Moreover, the three dimensional structure of the human alpha-thrombin-(hirugen).Dmc-azaLys acyl.enzyme complex has been analyzed and refined by X-ray crystallography at 2.0 A resolution (R-factor = 0.168). As observed for bovine beta-trypsin, the acylating inhibitor molecule is covalently bound to the Ser195 catalytic residue, filling the human alpha-thrombin S1 primary specificity subsite with its lysyl side-group. However, the carbonyl group of the scissile human alpha-thrombin.Dmc-azaLys acyl bond does not occupy properly the oxyanion binding hole. At variance from the bovine beta-trypsin.Dmc-azaLys acyl.enzyme structure, a second, not covalently bound, inhibitor molecule, partly shielded by the 60-insertion loop of human alpha-thrombin, is contacting the enzyme "aryl-binding site".
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1UMA is a Protein complex structure of sequences from Hirudo medicinalis and Homo sapiens with and as ligands. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
Reference
Human alpha-thrombin inhibition by the active site titrant N alpha-(N,N-dimethylcarbamoyl)-alpha-azalysine p-nitrophenyl ester: a comparative kinetic and X-ray crystallographic study., Nardini M, Pesce A, Rizzi M, Casale E, Ferraccioli R, Balliano G, Milla P, Ascenzi P, Bolognesi M, J Mol Biol. 1996 May 24;258(5):851-9. PMID:8637015
Page seeded by OCA on Thu Feb 21 15:26:07 2008
Categories: Hirudo medicinalis | Homo sapiens | Protein complex | Thrombin | Ascenzi, P. | Balliano, G. | Bolognesi, M. | Casale, E. | Ferraccioli, R. | Milla, P. | Nardini, M. | Pesce, A. | Rizzi, M. | IN2 | NAG | Alpha-thrombin | Hirugen complex (serine protease/inhibitor) | Hydrolase | Kringle | Serine protease
