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1lcy

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(New page: 200px<br /> <applet load="1lcy" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lcy, resolution 2.00&Aring;" /> '''Crystal Structure o...)
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'''Crystal Structure of the Mitochondrial Serine Protease HtrA2'''<br />
'''Crystal Structure of the Mitochondrial Serine Protease HtrA2'''<br />
==Overview==
==Overview==
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HtrA2/Omi, a mitochondrial serine protease in mammals, is important in, programmed cell death. However, the underlining mechanism of, HtrA2/Omi-mediated apoptosis remains unclear. Analogous to the bacterial, homolog HtrA (DegP), the mature HtrA2 protein contains a central serine, protease domain and a C-terminal PDZ domain. The 2.0 A crystal structure, of HtrA2/Omi reveals the formation of a pyramid-shaped homotrimer mediated, exclusively by the serine protease domains. The peptide-binding pocket of, the PDZ domain is buried in the intimate interface between the PDZ and the, protease domains. Mutational analysis reveals that the monomeric HtrA2/Omi, mutants are unable to induce cell death and are deficient in protease, activity. The PDZ domain modulates HtrA2/Omi-mediated cell death activity, by regulating its serine protease activity. These structural and, biochemical observations provide an important framework for deciphering, the mechanisms of HtrA2/Omi-mediated apoptosis.
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HtrA2/Omi, a mitochondrial serine protease in mammals, is important in programmed cell death. However, the underlining mechanism of HtrA2/Omi-mediated apoptosis remains unclear. Analogous to the bacterial homolog HtrA (DegP), the mature HtrA2 protein contains a central serine protease domain and a C-terminal PDZ domain. The 2.0 A crystal structure of HtrA2/Omi reveals the formation of a pyramid-shaped homotrimer mediated exclusively by the serine protease domains. The peptide-binding pocket of the PDZ domain is buried in the intimate interface between the PDZ and the protease domains. Mutational analysis reveals that the monomeric HtrA2/Omi mutants are unable to induce cell death and are deficient in protease activity. The PDZ domain modulates HtrA2/Omi-mediated cell death activity by regulating its serine protease activity. These structural and biochemical observations provide an important framework for deciphering the mechanisms of HtrA2/Omi-mediated apoptosis.
==Disease==
==Disease==
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==About this Structure==
==About this Structure==
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1LCY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1LCY OCA].
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1LCY is a [http://en.wikipedia.org/wiki/Single_protein 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=1LCY OCA].
==Reference==
==Reference==
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Alnemri, E.S.]]
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[[Category: Alnemri, E S.]]
[[Category: Chai, J.]]
[[Category: Chai, J.]]
[[Category: Li, P.]]
[[Category: Li, P.]]
[[Category: Li, W.]]
[[Category: Li, W.]]
[[Category: Shi, Y.]]
[[Category: Shi, Y.]]
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[[Category: Srinivasula, S.M.]]
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[[Category: Srinivasula, S M.]]
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[[Category: Wu, J.W.]]
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[[Category: Wu, J W.]]
[[Category: Zhang, Z.]]
[[Category: Zhang, Z.]]
[[Category: apoptosis]]
[[Category: apoptosis]]
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[[Category: serine protease]]
[[Category: serine protease]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:58:52 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:43:55 2008''

Revision as of 11:44, 21 February 2008


1lcy, resolution 2.00Å

Drag the structure with the mouse to rotate

Crystal Structure of the Mitochondrial Serine Protease HtrA2

Contents

Overview

HtrA2/Omi, a mitochondrial serine protease in mammals, is important in programmed cell death. However, the underlining mechanism of HtrA2/Omi-mediated apoptosis remains unclear. Analogous to the bacterial homolog HtrA (DegP), the mature HtrA2 protein contains a central serine protease domain and a C-terminal PDZ domain. The 2.0 A crystal structure of HtrA2/Omi reveals the formation of a pyramid-shaped homotrimer mediated exclusively by the serine protease domains. The peptide-binding pocket of the PDZ domain is buried in the intimate interface between the PDZ and the protease domains. Mutational analysis reveals that the monomeric HtrA2/Omi mutants are unable to induce cell death and are deficient in protease activity. The PDZ domain modulates HtrA2/Omi-mediated cell death activity by regulating its serine protease activity. These structural and biochemical observations provide an important framework for deciphering the mechanisms of HtrA2/Omi-mediated apoptosis.

Disease

Known diseases associated with this structure: Parkinson disease 13 OMIM:[606441]

About this Structure

1LCY is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi., Li W, Srinivasula SM, Chai J, Li P, Wu JW, Zhang Z, Alnemri ES, Shi Y, Nat Struct Biol. 2002 Jun;9(6):436-41. PMID:11967569

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