1yyy

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[[Image:1yyy.gif|left|200px]]<br /><applet load="1yyy" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1yyy.gif|left|200px]]
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caption="1yyy, resolution 2.1&Aring;" />
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'''TRYPSIN INHIBITORS WITH RIGID TRIPEPTIDYL ALDEHYDES'''<br />
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{{Structure
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|PDB= 1yyy |SIZE=350|CAPTION= <scene name='initialview01'>1yyy</scene>, resolution 2.1&Aring;
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|SITE= <scene name='pdbsite=CAT:Active+Site'>CAT</scene>
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|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=BNS:HYDROSULFONYLBENZENE'>BNS</scene> and <scene name='pdbligand=NVA:NORVALINE'>NVA</scene>
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|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]
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|GENE=
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}}
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'''TRYPSIN INHIBITORS WITH RIGID TRIPEPTIDYL ALDEHYDES'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1YYY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=BNS:'>BNS</scene> and <scene name='pdbligand=NVA:'>NVA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Site: <scene name='pdbsite=CAT:Active+Site'>CAT</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YYY OCA].
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1YYY is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YYY OCA].
==Reference==
==Reference==
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Highly selective mechanism-based thrombin inhibitors: structures of thrombin and trypsin inhibited with rigid peptidyl aldehydes., Krishnan R, Zhang E, Hakansson K, Arni RK, Tulinsky A, Lim-Wilby MS, Levy OE, Semple JE, Brunck TK, Biochemistry. 1998 Sep 1;37(35):12094-103. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9724521 9724521]
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Highly selective mechanism-based thrombin inhibitors: structures of thrombin and trypsin inhibited with rigid peptidyl aldehydes., Krishnan R, Zhang E, Hakansson K, Arni RK, Tulinsky A, Lim-Wilby MS, Levy OE, Semple JE, Brunck TK, Biochemistry. 1998 Sep 1;37(35):12094-103. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9724521 9724521]
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: hydrolase]]
[[Category: hydrolase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:10:29 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:29:13 2008''

Revision as of 13:29, 20 March 2008

Image:1yyy.gif


PDB ID 1yyy

Drag the structure with the mouse to rotate
, resolution 2.1Å
Sites:
Ligands: , and
Activity: Trypsin, with EC number 3.4.21.4
Coordinates: save as pdb, mmCIF, xml



TRYPSIN INHIBITORS WITH RIGID TRIPEPTIDYL ALDEHYDES


Overview

The crystal structures of three highly potent and selective low-molecular weight rigid peptidyl aldehyde inhibitors complexed with thrombin have been determined and refined to R values 0.152-0. 170 at 1.8-2.1 A resolution. Since the selectivity of two of the inhibitors was >1600 with respect to trypsin, the structures of trypsin-inhibited complexes of these inhibitors were also determined (R = 0.142-0.157 at 1.9-2.1 A resolution). The selectivity appears to reside in the inability of a benzenesulfonamide group to bind at the equivalent of the D-enantiomorphic S3 site of thrombin, which may be related to the lack of a 60-insertion loop in trypsin. All the inhibitors have a novel lactam moiety at the P3 position, while the two with greatest trypsin selectivity have a guanidinopiperidyl group at the P1 position that binds in the S1 specificity site. Differences in the binding constants of these inhibitors are correlated with their interactions with thrombin and trypsin. The kinetics of inhibition vary from slow to fast with thrombin and are fast in all cases with trypsin. The kinetics are examined in terms of the slow formation of a stable transition-state complex in a two-step mechanism. The structures of both thrombin and trypsin complexes show similar well-defined transition states in the S1 site and at the electrophilic carbon atom and Ser195OG. The trypsin structures, however, suggest that the first step in a two-step kinetic mechanism may involve formation of a weak transition-state complex, rather than binding dominated by the P2-P4 positions.

About this Structure

1YYY is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.

Reference

Highly selective mechanism-based thrombin inhibitors: structures of thrombin and trypsin inhibited with rigid peptidyl aldehydes., Krishnan R, Zhang E, Hakansson K, Arni RK, Tulinsky A, Lim-Wilby MS, Levy OE, Semple JE, Brunck TK, Biochemistry. 1998 Sep 1;37(35):12094-103. PMID:9724521

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