Binding of Streptomyces pepsin inhibitor (acetyl-pepstatin) with chymosin (rennin)

Nakatani, Hiroshi; Tsuchiya, Masakazu; Morita, Toshiteru; Ohki, S; Kitano, Hiromi

doi:10.1016/0005-2744(80)90175-8

Cited by 5 publications

(5 citation statements)

References 12 publications

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“…The activity of chymosin is affected by several environmental conditions, e.g., temperature, pH and ionic strength (see Crabbe, 2004;Dalgleish, 1992), and, like most aspartyl proteinases (Marciniszyn, Hartsuck, & Tang, 1976), chymosin is inhibited by pepstatin (Brinkhuis & Payens, 1985;Nakatani, Tsuchiya, Morita, Ohki, & Hiromi, 1980;Shakeel-Ur-Rehman, Feeney, McSweeney, & Fox, 1998). Whey proteins can also partially inhibit the hydrolysis of caseins by chymosin (Bech, 1993;Hayes, Kelly, & McSweeney, 2002).…”

Section: Introductionmentioning

confidence: 96%

Inhibition of the proteolytic activity of indigenous plasmin or exogenous chymosin and pepsin in bovine milk by blood serum

Huppertz

Uniacke

Kelly

et al. 2006

International Dairy Journal

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Section: Introductionmentioning

confidence: 96%

Inhibition of the proteolytic activity of indigenous plasmin or exogenous chymosin and pepsin in bovine milk by blood serum

Huppertz

Uniacke

Kelly

et al. 2006

International Dairy Journal

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“…Aspartyl proteases have a specific affinity for pepstatin. 52 Therefore, the increase in ∆I a and d∆E p values upon the incubation with pepsin could be attributed to the binding of enzyme to the pepstatin analogous groups in the SAM and concomitant increase in the average thickness of the adsorbed substance, which decelerated the diffusion of the probe, and consequently, increased the ∆I a and d∆E p values (Scheme 3). The inhibitory effect of pepstatin A on the initial increase in ∆E p value for the DTUA-Pepsta(h)/2-HEDS (9:1)-modified electrode (Figure 2C) suggested that the binding of pepsin to Pepsta(h) moieties was specific.…”

Section: Resultsmentioning

confidence: 99%

“…This family of enzymes is characterized by their inhibition with a low level of pepstatin (Pepstatin A, Iva-Val-Val-Sta-Ala-Sta) from Streptomyces sp. 52 The unit of statine (4-amino-3-hydroxy-6-methylheptanoic acid) in the pepstatin molecule resembles the tetrahedral intermediate in the hydrolysis of peptides, which results in the effective inhibition of catalyses by aspartyl proteases. 53 In this report, a SAM carrying a fragment of pepstatin was constructed on a gold surface, and recognition of the fragment at the SAM surface by proteolytic enzymes, pepsin and HIV-1 protease, was studied using both the LSPR-AS technique and the CV method with hydroquinone as a probe.…”

mentioning

confidence: 99%

“…This family of enzymes is characterized by their inhibition with a low level of pepstatin (Pepstatin A, Iva-Val-Val-Sta-Ala-Sta) from Streptomyces sp. The unit of statine (4-amino-3-hydroxy-6-methylheptanoic acid) in the pepstatin molecule resembles the tetrahedral intermediate in the hydrolysis of peptides, which results in the effective inhibition of catalyses by aspartyl proteases …”

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confidence: 99%

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Self-Assembled Monolayer of a Pepstatin Fragment as a Sensing Element for Aspartyl Proteases

et al. 2005

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A novel disulfide, which carried two pepstatin fragments at both ends, was prepared by the coupling of 11,11'-dithiobisundecanoic acid (DTUA) with a fragment (Val-Val-Sta) carrying a n-hexyl end (Pepsta(h)). The compound obtained (DTUA-Pepsta(h)) formed a self-assembled monolayer (SAM) on a gold electrode and vacuum-evaporated gold thin film as proven by cyclic voltammetry and reflection absorption infrared spectroscopy, respectively. When the SAM-modified gold electrode was incubated with a solution of aspartyl protease, pepsin, a decrease in both anodic and cathodic peak currents and an increase in potential difference were observed in the cyclic voltamogram of hydroquinone as a probe, whereas a coexistence of free pepstatin fragment inhibited these phenomena, indicating the specific binding of pepsin to the fragment at the exterior of the SAM. The binding rate of the enzyme to the SAM was largely dependent on the surface density of the fragment moiety in the SAM. Furthermore, when the SAM of DTUA-Pepsta(h) on a gold colloid array deposited on an amino group-modified glass plate was immersed in a pepsin solution, absorption of the glass plate at 550 nm corresponding to a localized surface plasmon resonance of the gold colloid abruptly increased and slightly red-shifted, and a further addition of pepstatin A gradually decreased the absorbance. From the increasing and decreasing profiles of absorbance, the association constant (K(assoc)) for pepsin with the fragment on the SAM was determined. Similar phenomena were observed upon immersion of the fragment-modified SAM in a solution of HIV-1 protease, suggesting a usability of the pepstatin fragment SAM for the detection and removal of the enzyme from biological fluids.

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“…By contrast, relatively little attention has been paid to the effects of changes at the N-terminal end of the molecule. Acetyl-pepstatin is as potent an inhibitor as the isovaleryl derivative (Nakatani et al, 1980;Satoi & Murao, 1971) and the shortened tetrapeptides, acetyl-Val-statyl-Ala-statine and isovaleryl-Val-statyl-Ala-statine are also very-tightbinding inhibitors of pig pepsin (Marciniszyn et al, 1976;Rich et al, 1980). These acylated tetrapeptides are just as poorly soluble in water as their parent pentapeptides, whereas by the simple expedient of introducing a hydrophilic lactoyl residue as the acylating group, the resultant blocked tetrapeptide (lactoyl-pepstatin) is rendered totally water-soluble.…”

mentioning

confidence: 99%

The effects of lactoyl-pepstatin and the pepsin inhibitor peptide on pig cathepsin D.

Kay¹,

Afting²,

Aoyagi³

et al. 1982

Biochemical Journal

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Lactoyl-pepstatin (an acylated tetrapeptide) is much more readily soluble in aqueous media than the more common isovaleryl- and acetyl-pepstatins (acylated pentapeptides). However, the K1 value for inhibition of cathepsin D by lactoyl-pepstatin at pH 3.5 is approx. 10(-7) M, some two to three orders of magnitude weaker than has been obtained previously for isovaleryl- or acetyl-pepstatins. One of the peptides released during activation of pig pepsinogen is known to be an effective inhibitor of pig pepsin, but it does not alter the activity of the similar aspartic proteinase, pig cathepsin D.

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Binding of Streptomyces pepsin inhibitor (acetyl-pepstatin) with chymosin (rennin)

Cited by 5 publications

References 12 publications

Inhibition of the proteolytic activity of indigenous plasmin or exogenous chymosin and pepsin in bovine milk by blood serum

Inhibition of the proteolytic activity of indigenous plasmin or exogenous chymosin and pepsin in bovine milk by blood serum

Self-Assembled Monolayer of a Pepstatin Fragment as a Sensing Element for Aspartyl Proteases

The effects of lactoyl-pepstatin and the pepsin inhibitor peptide on pig cathepsin D.

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