1sl3: Difference between revisions
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caption="1sl3, resolution 1.81Å" /> | caption="1sl3, resolution 1.81Å" /> | ||
'''crystal structue of Thrombin in complex with a potent P1 heterocycle-Aryl based inhibitor'''<br /> | '''crystal structue of Thrombin in complex with a potent P1 heterocycle-Aryl based inhibitor'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1SL3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with 170 as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | 1SL3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=170:'>170</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1SL3 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: thrombin inhibitor complex]] | [[Category: thrombin inhibitor complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:54:04 2008'' | ||
Revision as of 17:54, 15 February 2008
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crystal structue of Thrombin in complex with a potent P1 heterocycle-Aryl based inhibitor
OverviewOverview
In an effort to discover potent, clinically useful thrombin inhibitors, a, rapid analogue synthetic approach was used to explore the P(1) region., Various benzylamines were coupled to a pyridine/pyrazinone P(2)-P(3), template. One compound with an o-thiadiazole benzylic substitution was, found to have a thrombin K(i) of 0.84 nM. A study of ortho-substituted, five-membered-ring heterocycles was undertaken and subsequently, demonstrated that the o-triazole and tetrazole rings were optimal., Combination of these potent P(1) aryl heterocycles with a variety of, P(2)-P(3) groups produced a compound with an extraordinary thrombin, inhibitory activity of 1.4 pM. It is hoped that this potency enhancement, in P(1) will allow for more diversification in the P(2)-P(3) region to, ultimately address additional pharmacological concerns.
DiseaseDisease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this StructureAbout this Structure
1SL3 is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
ReferenceReference
Discovery and evaluation of potent P1 aryl heterocycle-based thrombin inhibitors., Young MB, Barrow JC, Glass KL, Lundell GF, Newton CL, Pellicore JM, Rittle KE, Selnick HG, Stauffer KJ, Vacca JP, Williams PD, Bohn D, Clayton FC, Cook JJ, Krueger JA, Kuo LC, Lewis SD, Lucas BJ, McMasters DR, Miller-Stein C, Pietrak BL, Wallace AA, White RB, Wong B, Yan Y, Nantermet PG, J Med Chem. 2004 Jun 3;47(12):2995-3008. PMID:15163182
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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Homo sapiens
- Single protein
- Thrombin
- Barrow, J.C.
- Bohn, D.
- Clayton, F.C.
- Cook, J.J.
- Glass, K.L.
- Krueger, J.A.
- Kuo, L.C.
- Lewis, S.D.
- Lucas, B.J.
- Lundell, G.F.
- McMasters, D.R.
- Miller-Stein, C.
- Newton, C.L.
- Pellicore, J.M.
- Pietrak, B.L.
- Rittle, K.E.
- Selnick, H.G.
- Stauffer, K.J.
- Vacca, J.P.
- Williams, P.D.
- Young, M.B.
- 170
- Thrombin inhibitor complex