[46] Acylamino acid-releasing enzyme from rat liver

Tsunasawa, Susumu; Narita, Kozo

doi:10.1016/s0076-6879(76)45049-8

Cited by 45 publications

(50 citation statements)

References 8 publications

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“…The tables have been organized to emphasize the negative effect of certain amino acid residues in certain positions of the substrates and also to reflect the general decrease in rate as the peptides grow longer. To evaluate the new data, it is important to summarize earlier observations (Tsunasawa et al, 1975;Gade & Brown, 1978;Jones & Manning, 1985;Kobayashi & Smith, 1987;Radhakrishna & Wold, 1989) regarding the specificity of this enzyme. Briefly, it has been shown that the enzyme requires one of five N-terminal acetylamino acids for rapid hydrolysis: Thr, Ala, Met, Ser, Gly; from comparison of peptides differing only in the N-terminal amino acid, it appears that Ac-Thr is cleaved 5-6 times faster than Ac-Gly, and the remaining three fall between these values in the order given.…”

Section: Resultsmentioning

confidence: 99%

“…The acylaminoacylpeptide hydrolases have been purified from rat liver (Tsunasawa et al, 1975;Kobayashi & Smith, 1987), bovine liver (Gade & Brown, 1978), pig liver (Mitta et al, 1989), human erythrocytes (Schonberger & Tschesche, 1981; Jones & Manning, 1985), and sheep erythrocytes (Witheiler & Wilson, 1972), and a good deal of information about the molecular and catalytic properties of these enzymes as well as of the present muscle enzyme (Radhakrishna & Wold, 1989, 1990) has been reported. Although there are many conflicts in detail, the specificities of the different hydrolase preparations have certain common features.…”

Section: Discussionmentioning

confidence: 99%

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Specificity determinants of acylaminoacyl‐peptide hydrolase

Krishna

Wold

1992

Protein Science

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In an attempt to explore how specific features of the substrate's primary structure may affect the activity of rabbit muscle acylaminoacyl-peptide hydrolase (EC 3.4.19. l), a number of acetylated peptides containing specific amino acid replacements in specific positions were prepared and compared as substrates for the hydrolase. The principal variants were D-Ala, Pro, and positive charges (His, Arg, Lys); in addition, the effect of the length of the peptide was also investigated in a less systematic manner. The substrates were either prepared by direct acetylation of peptides, by extension of the N-terminus with acetylamino acids or acetylpeptides, activated as Nhydroxysuccinimide esters, or by isolation of the N-terminal peptides from naturally occurring acetylated proteins.It was found that D-Ala on either side of the bond to be cleaved (positions 1 and 2) completely inhibited the enzymatic activity, whereas acetylated peptides with D-Ala in positions 3 or 4 were as good substrates as those containing L-Ala. Peptides with Pro in positions 2 were also inactive, and most of the peptides with Pro in the third position were very poor substrates; only the peptide Ac-AAP gave reasonably high activity (30% of Ac-AAA), which was reduced to 1-2070 if additional residues were present at the C-terminus (Ac-AAPA, Ac-AAPAA). The presence of a positive charge in positions 2, 3 , 4 , 5 , and 6 gave strong reduction in hydrolase activity varying with the charge's distance from the N-terminus from 0 to 15-20% of the rates obtained with the reference peptides without positive charges. Deprotonation of His at high pH generated excellent substrates, and removal of the positive charges of Lys by acetylation or, even better, succinylation also gave improved substrate quality, demonstrating that the positive charges are responsible for the inhibition. Long peptides (10-29 residues) were generally found to be poor substrates, especially when they contained positive charges and Pro. The better long peptide substrates d o not have these residues, but contain negative charges instead. A survey of the N-terminal sequences of more than 100 acetylated proteins revealed that about 95% of them have Pro and/or positively charged amino acids among the first 10 residues, suggesting that these residues may be natural inhibitors of hydrolase action in vivo. In addition to the specific and large effect of the residues described above on substrate quality, it also appears that there is a general effect of the overall sequence of each peptide, and that the specific effects of individual residues are modulated significantly by the environment (context) in which they are expressed.Keywords: acetylated N-termini; acylaminoacyl-peptide hydrolase; N-terminal processing; posttranslational modification; primary sequence specificity determinants A large number of chemical modifications of proteins transport, and during proteolytic destruction. Most of take place in living cells both during co-and posttransthese reactions are characterized by an extr...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Specificity determinants of acylaminoacyl‐peptide hydrolase

Krishna

Wold

1992

Protein Science

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“…Acylpeptide hydrolase (APH) is a tetrameric enzyme protein of 300 kDa which belongs to a new class of serine-type peptidases that are relatively large in molecular size (Tsunasawa, Narita and Ogata, 1975;Kobayashi and Smith, 1987;Scaloni et al, 1992). Under denaturing conditions the native 300 kDa protein dissociates into 75 kDa subunits, each having one active site (Kobayashi and Smith 1987;Scaloni et al, 1992;Sharma and Ortwerth, 1993).…”

Section: Introductionmentioning

confidence: 99%

Studies on Trypsin-modified Bovine and Human Lens Acylpeptide Hydrolase

Senthilkumar

Reddy

Sharma

2001

Experimental Eye Research

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“…APH, also known as acylamino acid-releasing enzyme (AARE; EC 3.4.19.1), is a tetrameric enzyme protein of 300 kDa and a member of the prolyl oligopeptidase family (41). APH catalyzes the hydrolysis of N-acetylated peptide to an acyl amino acid and to a peptide with a free N terminus shortened by one amino acid residue (42). However, the enzyme cannot remove acetylated NH 2 -terminal residues from structural proteins such as crystallins (43,44).…”

mentioning

confidence: 99%

Lens Crystallin Modifications and Cataract in Transgenic Mice Overexpressing Acylpeptide Hydrolase

Santhoshkumar¹,

Xie

Raju

et al. 2014

Journal of Biological Chemistry

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Background: Acylpeptide hydrolase (APH) in the lens may have an integral role in cataract formation. Results: Transgenic overexpression of APH results in crystallin cleavage, impaired lens development, and cataract. Conclusion: APH may be involved in the generation of peptides that have the potential to induce protein aggregation. Significance: The transgenic APH mouse model could help us understand the role of crystallin fragments in cataractogenesis.

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[46] Acylamino acid-releasing enzyme from rat liver

Cited by 45 publications

References 8 publications

Specificity determinants of acylaminoacyl‐peptide hydrolase

Specificity determinants of acylaminoacyl‐peptide hydrolase

Studies on Trypsin-modified Bovine and Human Lens Acylpeptide Hydrolase

Lens Crystallin Modifications and Cataract in Transgenic Mice Overexpressing Acylpeptide Hydrolase

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