2ra3
From Proteopedia
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| - | [[Image:2ra3.jpg|left|200px]] | + | [[Image:2ra3.jpg|left|200px]] |
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| - | '''Human cationic trypsin complexed with bovine pancreatic trypsin inhibitor (BPTI)''' | + | {{Structure |
| + | |PDB= 2ra3 |SIZE=350|CAPTION= <scene name='initialview01'>2ra3</scene>, resolution 1.46Å | ||
| + | |SITE= <scene name='pdbsite=AC1:Ca+Binding+Site+For+Residue+A+1'>AC1</scene>, <scene name='pdbsite=AC2:So4+Binding+Site+For+Residue+A+6'>AC2</scene>, <scene name='pdbsite=AC3:So4+Binding+Site+For+Residue+A+10'>AC3</scene>, <scene name='pdbsite=AC4:So4+Binding+Site+For+Residue+A+12'>AC4</scene>, <scene name='pdbsite=AC5:So4+Binding+Site+For+Residue+A+14'>AC5</scene>, <scene name='pdbsite=AC6:So4+Binding+Site+For+Residue+A+247'>AC6</scene>, <scene name='pdbsite=AC7:So4+Binding+Site+For+Residue+A+248'>AC7</scene>, <scene name='pdbsite=AC8:So4+Binding+Site+For+Residue+A+249'>AC8</scene>, <scene name='pdbsite=AC9:Ca+Binding+Site+For+Residue+B+1'>AC9</scene>, <scene name='pdbsite=BC1:So4+Binding+Site+For+Residue+B+4'>BC1</scene>, <scene name='pdbsite=BC2:So4+Binding+Site+For+Residue+B+5'>BC2</scene>, <scene name='pdbsite=BC3:So4+Binding+Site+For+Residue+B+7'>BC3</scene>, <scene name='pdbsite=BC4:So4+Binding+Site+For+Residue+B+8'>BC4</scene>, <scene name='pdbsite=BC5:So4+Binding+Site+For+Residue+B+11'>BC5</scene>, <scene name='pdbsite=BC6:So4+Binding+Site+For+Residue+B+15'>BC6</scene>, <scene name='pdbsite=BC7:So4+Binding+Site+For+Residue+B+247'>BC7</scene>, <scene name='pdbsite=BC8:So4+Binding+Site+For+Residue+B+248'>BC8</scene>, <scene name='pdbsite=BC9:So4+Binding+Site+For+Residue+B+249'>BC9</scene>, <scene name='pdbsite=CC1:So4+Binding+Site+For+Residue+B+250'>CC1</scene>, <scene name='pdbsite=CC2:So4+Binding+Site+For+Residue+I+59'>CC2</scene>, <scene name='pdbsite=CC3:So4+Binding+Site+For+Residue+I+60'>CC3</scene>, <scene name='pdbsite=CC4:So4+Binding+Site+For+Residue+I+61'>CC4</scene>, <scene name='pdbsite=CC5:So4+Binding+Site+For+Residue+I+62'>CC5</scene>, <scene name='pdbsite=CC6:So4+Binding+Site+For+Residue+I+63'>CC6</scene>, <scene name='pdbsite=CC7:So4+Binding+Site+For+Residue+C+59'>CC7</scene> and <scene name='pdbsite=CC8:So4+Binding+Site+For+Residue+C+60'>CC8</scene> | ||
| + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> and <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] | ||
| + | |GENE= PRSS1, TRP1, TRY1, TRYP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Human cationic trypsin complexed with bovine pancreatic trypsin inhibitor (BPTI)''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2RA3 is a [ | + | 2RA3 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RA3 OCA]. |
==Reference== | ==Reference== | ||
| - | Structural Basis for Accelerated Cleavage of Bovine Pancreatic Trypsin Inhibitor (BPTI) by Human Mesotrypsin., Salameh MA, Soares AS, Hockla A, Radisky ES, J Biol Chem. 2008 Feb 15;283(7):4115-23. Epub 2007 Dec 12. PMID:[http:// | + | Structural Basis for Accelerated Cleavage of Bovine Pancreatic Trypsin Inhibitor (BPTI) by Human Mesotrypsin., Salameh MA, Soares AS, Hockla A, Radisky ES, J Biol Chem. 2008 Feb 15;283(7):4115-23. Epub 2007 Dec 12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18077447 18077447] |
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: zymogen]] | [[Category: zymogen]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:33:56 2008'' |
Revision as of 16:33, 20 March 2008
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| , resolution 1.46Å | |||||||
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| Sites: | , , , , , , , , , , , , , , , , , , , , , , , , and | ||||||
| Ligands: | and | ||||||
| Gene: | PRSS1, TRP1, TRY1, TRYP1 (Homo sapiens) | ||||||
| Activity: | Trypsin, with EC number 3.4.21.4 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human cationic trypsin complexed with bovine pancreatic trypsin inhibitor (BPTI)
Overview
Human mesotrypsin is an isoform of trypsin that displays unusual resistance to polypeptide trypsin inhibitors and has been observed to cleave several such inhibitors as substrates. Whereas substitution of arginine for the highly conserved glycine 193 in the trypsin active site has been implicated as a critical factor in the inhibitor resistance of mesotrypsin, how this substitution leads to accelerated inhibitor cleavage is not clear. Bovine pancreatic trypsin inhibitor (BPTI) forms an extremely stable and cleavage-resistant complex with trypsin, and thus provides a rigorous challenge of mesotrypsin catalytic activity toward polypeptide inhibitors. Here, we report kinetic constants for mesotrypsin and the highly homologous (but inhibitor sensitive) human cationic trypsin, describing inhibition by, and cleavage of BPTI, as well as crystal structures of the mesotrypsin-BPTI and human cationic trypsin-BPTI complexes. We find that mesotrypsin cleaves BPTI with a rate constant accelerated 350-fold over that of human cationic trypsin and 150,000-fold over that of bovine trypsin. From the crystal structures, we see that small conformational adjustments limited to several side chains enable mesotrypsin-BPTI complex formation, surmounting the predicted steric clash introduced by Arg-193. Our results show that the mesotrypsin-BPTI interface favors catalysis through (a) electrostatic repulsion between the closely spaced mesotrypsin Arg-193 and BPTI Arg-17, and (b) elimination of two hydrogen bonds between the enzyme and the amine leaving group portion of BPTI. Our model predicts that these deleterious interactions accelerate leaving group dissociation and deacylation.
About this Structure
2RA3 is a Protein complex structure of sequences from Bos taurus and Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural Basis for Accelerated Cleavage of Bovine Pancreatic Trypsin Inhibitor (BPTI) by Human Mesotrypsin., Salameh MA, Soares AS, Hockla A, Radisky ES, J Biol Chem. 2008 Feb 15;283(7):4115-23. Epub 2007 Dec 12. PMID:18077447
Page seeded by OCA on Thu Mar 20 18:33:56 2008
Categories: Bos taurus | Homo sapiens | Protein complex | Trypsin | Radisky, E S. | Salameh, M A. | Soares, A S. | CA | SO4 | Bovine pancreatic trypsin inhibitor | Bpti | Calcium | Digestion | Disease mutation | Human cationic trypsin | Hydrolase | Hydrolase/hydrolase inhibitor complex | Metal-binding | Pharmaceutical | Protease inhibitor | Secreted | Serine protease | Serine protease inhibitor | Sulfation | Zymogen
