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1lcy

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1lcy, resolution 2.00Å

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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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