1b7x
From Proteopedia
(New page: 200px<br /> <applet load="1b7x" size="450" color="white" frame="true" align="right" spinBox="true" caption="1b7x, resolution 2.10Å" /> '''STRUCTURE OF HUMAN ...) |
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'''STRUCTURE OF HUMAN ALPHA-THROMBIN Y225I MUTANT BOUND TO D-PHE-PRO-ARG-CHLOROMETHYLKETONE'''<br /> | '''STRUCTURE OF HUMAN ALPHA-THROMBIN Y225I MUTANT BOUND TO D-PHE-PRO-ARG-CHLOROMETHYLKETONE'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1B7X is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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:// | + | 1B7X is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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=1B7X 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 Fri Feb 15 15:31:12 2008'' |
Revision as of 13:31, 15 February 2008
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STRUCTURE OF HUMAN ALPHA-THROMBIN Y225I MUTANT BOUND TO D-PHE-PRO-ARG-CHLOROMETHYLKETONE
Contents |
Overview
Residue 225 in serine proteases of the chymotrypsin family is Pro or Tyr, in more than 95% of nearly 300 available sequences. Proteases with Y225, (like some blood coagulation and complement factors) are almost, exclusively found in vertebrates, whereas proteases with P225 (like, degradative enzymes) are present from bacteria to human. Saturation, mutagenesis of Y225 in thrombin shows that residue 225 affects ligand, recognition up to 60,000-fold. With the exception of Tyr and Phe, all, residues are associated with comparable or greatly reduced catalytic, activity relative to Pro. The crystal structures of three mutants that, differ widely in catalytic activity (Y225F, Y225P, and Y225I) show that, although residue 225 makes no contact with substrate, it drastically, influences the shape of the water channel around the primary specificity, site. The activity profiles obtained for thrombin also suggest that the, conversion of Pro to Tyr or Phe documented in the vertebrates occurred, through Ser and was driven by a significant gain (up to 50-fold) in, catalytic activity. In fact, Ser and Phe are documented in 4% of serine, proteases, which together with Pro and Tyr account for almost the entire, distribution of residues at position 225. The unexpected crucial role of, residue 225 in serine proteases explains the evolutionary selection of, residues at this position and shows that the structural determinants of, protease activity and specificity are more complex than currently, believed. These findings have broad implications in the rational design of, enzymes with enhanced catalytic properties.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1B7X is a Protein complex structure of sequences from Homo sapiens. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
Reference
Unexpected crucial role of residue 225 in serine proteases., Guinto ER, Caccia S, Rose T, Futterer K, Waksman G, Di Cera E, Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):1852-7. PMID:10051558
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