2vj8
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:2vj8.jpg|left|200px]] | + | [[Image:2vj8.jpg|left|200px]] |
| - | + | ||
| - | '''COMPLEX OF HUMAN LEUKOTRIENE A4 HYDROLASE WITH A HYDROXAMIC ACID INHIBITOR''' | + | {{Structure |
| + | |PDB= 2vj8 |SIZE=350|CAPTION= <scene name='initialview01'>2vj8</scene>, resolution 1.8Å | ||
| + | |SITE= <scene name='pdbsite=AC1:Zn+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:Yb+Binding+Site+For+Chain+A'>AC2</scene>, <scene name='pdbsite=AC3:Yb+Binding+Site+For+Chain+A'>AC3</scene>, <scene name='pdbsite=AC4:Yb+Binding+Site+For+Chain+A'>AC4</scene>, <scene name='pdbsite=AC5:Imd+Binding+Site+For+Chain+A'>AC5</scene>, <scene name='pdbsite=AC6:Act+Binding+Site+For+Chain+A'>AC6</scene> and <scene name='pdbsite=AC7:Ha2+Binding+Site+For+Chain+A'>AC7</scene> | ||
| + | |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=YB:YTTERBIUM+(III)+ION'>YB</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene> and <scene name='pdbligand=HA2:6-[{(2S)-2-AMINO-3-[4-(BENZYLOXY)PHENYL]PROPYL}(HYDROXY)AMINO]-6-OXOHEXANOIC ACID)'>HA2</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Leukotriene-A(4)_hydrolase Leukotriene-A(4) hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.2.6 3.3.2.6] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''COMPLEX OF HUMAN LEUKOTRIENE A4 HYDROLASE WITH A HYDROXAMIC ACID INHIBITOR''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2VJ8 is a [ | + | 2VJ8 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VJ8 OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal structures of leukotriene A4 hydrolase in complex with captopril and two competitive tight-binding inhibitors., Thunnissen MM, Andersson B, Samuelsson B, Wong CH, Haeggstrom JZ, FASEB J. 2002 Oct;16(12):1648-50. Epub 2002 Aug 7. PMID:[http:// | + | Crystal structures of leukotriene A4 hydrolase in complex with captopril and two competitive tight-binding inhibitors., Thunnissen MM, Andersson B, Samuelsson B, Wong CH, Haeggstrom JZ, FASEB J. 2002 Oct;16(12):1648-50. Epub 2002 Aug 7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12207002 12207002] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Leukotriene-A(4) hydrolase]] | [[Category: Leukotriene-A(4) hydrolase]] | ||
| Line 31: | Line 40: | ||
[[Category: zinc]] | [[Category: zinc]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:47:10 2008'' |
Revision as of 16:47, 20 March 2008
| |||||||
| , resolution 1.8Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , , , , , and | ||||||
| Ligands: | , , , and | ||||||
| Activity: | Leukotriene-A(4) hydrolase, with EC number 3.3.2.6 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
COMPLEX OF HUMAN LEUKOTRIENE A4 HYDROLASE WITH A HYDROXAMIC ACID INHIBITOR
Overview
Leukotriene (LT) A4 hydrolase/aminopeptidase is a bifunctional zinc enzyme that catalyzes the final step in the biosynthesis of LTB4, a potent chemoattractant and immune modulating lipid mediator. Here, we report a high-resolution crystal structure of LTA4 hydrolase in complex with captopril, a classical inhibitor of the zinc peptidase angiotensin-converting enzyme. Captopril makes few interactions with the protein, but its free thiol group is bound to the zinc, apparently accounting for most of its inhibitory action on LTA4 hydrolase. In addition, we have determined the structures of LTA4 hydrolase in complex with two selective tight-binding inhibitors, a thioamine and a hydroxamic acid. Their common benzyloxyphenyl tail, designed to mimic the carbon backbone of LTA4, binds into a narrow hydrophobic cavity in the protein. The free hydroxyl group of the hydroxamic acid makes a suboptimal, monodentate complex with the zinc, and strategies for improved inhibitor design can be deduced from the structure. Taken together, the three crystal structures provide the molecular basis for the divergent pharmacological profiles of LTA4 hydrolase inhibitors. Moreover, they help define the binding pocket for the fatty acid-derived epoxide LTA4 as well as the subsites for a tripeptide substrate, which in turn have important implications for the molecular mechanisms of enzyme catalyses.
About this Structure
2VJ8 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structures of leukotriene A4 hydrolase in complex with captopril and two competitive tight-binding inhibitors., Thunnissen MM, Andersson B, Samuelsson B, Wong CH, Haeggstrom JZ, FASEB J. 2002 Oct;16(12):1648-50. Epub 2002 Aug 7. PMID:12207002
Page seeded by OCA on Thu Mar 20 18:47:10 2008
Categories: Homo sapiens | Leukotriene-A(4) hydrolase | Single protein | Andersson, B. | Haeggstrom, J Z. | Samuelsson, B. | Thunnissen, M M.G M. | Wong, C H. | ACT | HA2 | IMD | YB | ZN | Hydrolase | Hydroxamic acid | Leukotriene hydrolase | Metalloprotease | Protease | Zinc
