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2j83

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==Overview==
==Overview==
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Human pappalysin-1 is a multi-domain metalloprotease engaged in the, homeostasis of insulin-like growth factors and the founding member of the, pappalysin family within the metzincin clan of metalloproteases. We have, recently identified an archaeal relative, ulilysin, encompassing only the, protease domain. It is a 262-residue active protease with a novel 3D, structure with two subdomains separated by an active-site cleft. Despite, negligible overall sequence similarity, noticeable similarity is found, with other metzincin prototypes, adamalysins/ADAMs and matrix, metalloproteinases. Ulilysin has been crystallised in a product complex, with an arginine-valine dipeptide occupying the active-site S(1') and, S(2') positions and in a complex with the broad-spectrum hydroxamic, acid-based ... [[http://ispc.weizmann.ac.il/pmbin/getpm?17097044 (full description)]]
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Human pappalysin-1 is a multi-domain metalloprotease engaged in the, homeostasis of insulin-like growth factors and the founding member of the, pappalysin family within the metzincin clan of metalloproteases. We have, recently identified an archaeal relative, ulilysin, encompassing only the, protease domain. It is a 262-residue active protease with a novel 3D, structure with two subdomains separated by an active-site cleft. Despite, negligible overall sequence similarity, noticeable similarity is found, with other metzincin prototypes, adamalysins/ADAMs and matrix, metalloproteinases. Ulilysin has been crystallised in a product complex, with an arginine-valine dipeptide occupying the active-site S(1') and, S(2') positions and in a complex with the broad-spectrum hydroxamic, acid-based metalloprotease inhibitor, batimastat. This molecule inhibits, mature ulilysin with an IC(50) value of 61 microM under the conditions, assayed. The binding of batimastat to ulilysin evokes binding to, vertebrate matrix metalloproteases but is much weaker. These data give, insight into substrate specificity and mechanism of action and inhibition, of the novel pappalysin family.
==About this Structure==
==About this Structure==
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2J83 is a [[http://en.wikipedia.org/wiki/Single_protein Single protein]] structure of sequence from [[http://en.wikipedia.org/wiki/Methanosarcina_acetivorans Methanosarcina acetivorans]] with CA, ZN, BAT and GOL as [[http://en.wikipedia.org/wiki/ligands ligands]]. Structure known Active Site: AC1. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2J83 OCA]].
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2J83 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Methanosarcina_acetivorans Methanosarcina acetivorans] with CA, ZN, BAT and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2J83 OCA].
==Reference==
==Reference==
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[[Category: pappalysin]]
[[Category: pappalysin]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Oct 30 17:26:45 2007''
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 15:30:30 2007''

Revision as of 13:25, 5 November 2007


2j83, resolution 2.00Å

Drag the structure with the mouse to rotate

ULILYSIN METALLOPROTEASE IN COMPLEX WITH BATIMASTAT.

Overview

Human pappalysin-1 is a multi-domain metalloprotease engaged in the, homeostasis of insulin-like growth factors and the founding member of the, pappalysin family within the metzincin clan of metalloproteases. We have, recently identified an archaeal relative, ulilysin, encompassing only the, protease domain. It is a 262-residue active protease with a novel 3D, structure with two subdomains separated by an active-site cleft. Despite, negligible overall sequence similarity, noticeable similarity is found, with other metzincin prototypes, adamalysins/ADAMs and matrix, metalloproteinases. Ulilysin has been crystallised in a product complex, with an arginine-valine dipeptide occupying the active-site S(1') and, S(2') positions and in a complex with the broad-spectrum hydroxamic, acid-based metalloprotease inhibitor, batimastat. This molecule inhibits, mature ulilysin with an IC(50) value of 61 microM under the conditions, assayed. The binding of batimastat to ulilysin evokes binding to, vertebrate matrix metalloproteases but is much weaker. These data give, insight into substrate specificity and mechanism of action and inhibition, of the novel pappalysin family.

About this Structure

2J83 is a Single protein structure of sequence from Methanosarcina acetivorans with CA, ZN, BAT and GOL as ligands. Structure known Active Site: AC1. Full crystallographic information is available from OCA.

Reference

Substrate specificity of a metalloprotease of the pappalysin family revealed by an inhibitor and a product complex., Garcia-Castellanos R, Tallant C, Marrero A, Sola M, Baumann U, Gomis-Ruth FX, Arch Biochem Biophys. 2007 Jan 1;457(1):57-72. Epub 2006 Oct 24. PMID:17097044

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