1mq6: Difference between revisions
New page: left|200px<br /> <applet load="1mq6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mq6, resolution 2.10Å" /> '''Crystal Structure o... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1mq6. | [[Image:1mq6.jpg|left|200px]]<br /><applet load="1mq6" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1mq6" size=" | |||
caption="1mq6, resolution 2.10Å" /> | caption="1mq6, resolution 2.10Å" /> | ||
'''Crystal Structure of 3-chloro-N-[4-chloro-2-[[(5-chloro-2-pyridinyl)amino]carbonyl]-6-methoxyphenyl]-4-[[(4,5-dihydro-2-oxazolyl)methylamino]methyl]-2-thiophenecarboxamide Complexed with Human Factor Xa'''<br /> | '''Crystal Structure of 3-chloro-N-[4-chloro-2-[[(5-chloro-2-pyridinyl)amino]carbonyl]-6-methoxyphenyl]-4-[[(4,5-dihydro-2-oxazolyl)methylamino]methyl]-2-thiophenecarboxamide Complexed with Human Factor Xa'''<br /> | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
1MQ6 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA, XLD and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Coagulation_factor_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] Full crystallographic information is available from [http:// | 1MQ6 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=XLD:'>XLD</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Coagulation_factor_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MQ6 OCA]. | ||
==Reference== | ==Reference== | ||
| Line 27: | Line 26: | ||
[[Category: protein inhibitor complex]] | [[Category: protein inhibitor complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:25:19 2008'' | ||
Revision as of 17:25, 15 February 2008
|
Crystal Structure of 3-chloro-N-[4-chloro-2-[[(5-chloro-2-pyridinyl)amino]carbonyl]-6-methoxyphenyl]-4-[[(4,5-dihydro-2-oxazolyl)methylamino]methyl]-2-thiophenecarboxamide Complexed with Human Factor Xa
OverviewOverview
There has been intense interest in the development of factor Xa inhibitors, for the treatment of thrombotic diseases. Our laboratory has developed a, series of novel non-amidine inhibitors of factor Xa. This paper presents, two crystal structures of compounds from this series bound to factor Xa., The first structure is derived from the complex formed between factor Xa, and compound 1. Compound 1 was the first non-amidine factor Xa inhibitor, from our lab that had measurable potency in an in vitro assay of, anticoagulant activity. The second compound, 2, has a molar affinity for, factor Xa (K(iapp)) of 7 pM and good bioavailability. The two inhibitors, bind in an L-shaped conformation with a chloroaromatic ring buried deeply, in the S1 pocket. The opposite end of these compounds contains a basic, substituent that extends into the S4 binding site. A chlorinated phenyl, ring bridges the substituents in the S1 and S4 pockets via amide linkers., The overall conformation is similar to the previously published structures, for amidine-based inhibitors complexed with factor Xa. However, there are, significant differences in the interactions between the inhibitor and the, protein at the atomic level. Most notably, there is no group that forms a, salt bridge with the carboxylic acid at the base of the S1 pocket, (Asp189). Each inhibitor forms only one well-defined hydrogen bond to the, protein. There are no direct charge-charge interactions. The results, indicate that electrostatic interactions play a secondary role in the, binding of these potent inhibitors.
DiseaseDisease
Known disease associated with this structure: Factor X deficiency OMIM:[227600]
About this StructureAbout this Structure
1MQ6 is a Protein complex structure of sequences from Homo sapiens with , and as ligands. Active as Coagulation factor Xa, with EC number 3.4.21.6 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of two potent nonamidine inhibitors bound to factor Xa., Adler M, Kochanny MJ, Ye B, Rumennik G, Light DR, Biancalana S, Whitlow M, Biochemistry. 2002 Dec 31;41(52):15514-23. PMID:12501180
Page seeded by OCA on Fri Feb 15 16:25:19 2008