Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.64 (MPP)
 1,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mitochondrial processing enzyme consists of two components, the mitochondrial processing peptidase (MPP) and processing enhancing protein (PEP). MPP and PEP act cooperatively in proteolytic processing of mitochondrial precursor proteins. Most of the mitochondrial precursors possess aminoterminal presequences (also called "targeting sequences" or "signal sequences"), that do not display a common motif and that show only limited similarities of the cleavage sites. The mitochondrial processing peptidase is a metal-dependent endoprotease, sensitive to sulfhydryl-modifying reagents and appears to belong to a new class of proteases. MPP and PEP, together with the core 1 and core 2 proteins of the respiratory complex III, form a new protein family.
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PMID:Processing of mitochondrial precursor proteins. 183 52

Targeting signals of mitochondrial precursors are cleaved in the matrix during or after import by the mitochondrial processing peptidase (MPP). This enzyme consists of two nonidentical alpha- and beta-subunits each of molecular weight of about 50 kDa. In mammals and fungi, MPP is soluble in the matrix, whereas in plants the enzyme is part of the cytochrome bc1 complex. MPP is a metalloendopeptidase which has been classified as a member of the pitrilysin family on the basis of the HXXEHX76E zinc-binding motif present in beta-MPP. Both subunits of MPP are required for processing activity. The alpha-subunit of MPP, which probably recognizes a three-dimensional motif adopted by the presequence, presents the presequence to beta-MPP, which carries the catalytic active site. MPP acts as an endoprotease on chemically synthesized peptides corresponding to mitochondrial presequences. Matrix-targeting signals and MPP cleavage signals seem to be distinct, although the two signals may overlap within a given presequence. The structural element helix-turn-helix, that cleavable presequences adopt in a membrane mimetic environment, may be required for processing but is not sufficient for proteolysis. Binding of the presequence by alpha-MPP tolerates a high degree of mutations of the presequence. alpha-MPP may present a degenerated cleavage site motif to beta-MPP in an accessible conformation for processing. The conformation of mitochondrial presequences bound to MPP remains largely unknown.
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PMID:The mitochondrial processing peptidase: function and specificity. 898 49

The erythroid isoform of aminolevulinate synthase (eALAS) protein is a major control point in erythroid heme synthesis and hemoglobin formation. Erythroid cells were extracted from mouse blood and bone marrow and metabolically labeled with (35)S-methionine. This was followed by immunoprecipitation of eALAS protein products. The results show that the N-terminus of the expected full-length 59-kd form of the eALAS protein is truncated in bone marrow erythroid cells by approximately 7 kd. More differentiated erythroid cells in the peripheral blood exhibit very little of this protein truncation. Erythroid cells from the bone marrow were isolated using monoclonal antibody TER-119 and were shown to contain a unique endoprotease activity that could cleave the eALAS protein to the shorter form in vitro. With or without the mitochondrial signal sequence, the eALAS protein could serve as a substrate for the cleavage. This cleavage renders a functional eALAS protein and only removes a domain of unclear function, which has previously been reported to vary in size as a result of alternative RNA splicing. The protease activity was enriched from the membranes of mitochondria from bone marrow cells and was shown to be different from mitochondrial processing peptidase, medullasin, and other known proteases. Apart from the mitochondrial processing peptidase that cleaves the import signal sequence, this is the first description of a mitochondrially located site-specific processing protease activity. (Blood. 2000;96:740-746)
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PMID:A novel endoproteolytic processing activity in mitochondria of erythroid cells and the role in heme synthesis. 1088 43