X-ray diffraction analysis of porcine pepsin structure

Andreeva, N. S.; Zdanov, A.A.; Gustchina, Alla; Fedorov, A. E.

doi:10.1515/9783111649788-018

Cited by 15 publications

(20 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…l), which were originally identified by active-site-directed reagents: diazoacetylnorleucine methyl ester [ 121 and 1,2-epoxy-3-(p-nitrophenoxy) propane [ 131. These two aspartyl side chains, which are located in the center of the apparent substrate binding cleft, are within the hydrogen bond distance of each other [4,6,7,11] and are in essentially the same relationship in all four crystals. This high conformational similarity among the four extends also to the polypeptide chains near the active-site aspartyls.…”

Section: Evolution Of the Active Centermentioning

confidence: 83%

See 1 more Smart Citation

Evolution in the structure and function of aspartic proteases

Tang

Wong

1987

J of Cellular Biochemistry

290

194

View full text Add to dashboard Cite

Aspartic proteases (EC3.4.23) are a group of proteolytic enzymes of the pepsin family that share the same catalytic apparatus and usually function in acid solutions. This latter aspect limits the function of aspartic proteases to some specific locations in different organisms; thus the occurrence of aspartic proteases is less abundant than other groups of proteases, such as serine proteases. The best known sources of aspartic proteases are stomach (for pepsin, gastricsin, and chymosin), lysosomes (for cathepsins D and E), kidney (for renin), yeast granules, and fungi (for secreted proteases such as rhizopuspepsin, penicillopepsin, and endothiapepsin). These aspartic proteases have been extensively studied for their structure and function relationships and have been the topics of several reviews or monographs (Tang: Acid Proteases, Structure, Function and Biology. New York: Plenum Press, 1977; Tang: J Mol Cell Biochem 26:93-109, 1979; Kostka: Aspartic Proteinases and Their Inhibitors. Berlin: Walter de Gruyter, 1985). All mammalian aspartic proteases are synthesized as zymogens and are subsequently activated to active proteases. Although a zymogen for a fungal aspartic protease has not been found, the cDNA structure of rhizopuspepsin suggests the presence of a "pro" enzyme (Wong et al: Fed Proc 44:2725, 1985). It is probable that other fungal aspartic proteases are also synthesized as zymogens. It is the aim of this article to summarize the major models of structure-function relationships of aspartic proteases and their zymogens with emphasis on more recent findings. Attempts will also be made to relate these models to other aspartic proteases.

show abstract

Section: Evolution Of the Active Centermentioning

confidence: 83%

“…Pepsin (or pepsin A, EC3.4.23.1) from several species has been sequenced (see Fig. l), but the pig enzyme is the only gastric protease for which a high resolution crystal structure exists [4]. Gastricsin (or pepsin C, EC3.4.23.3) differs from pepsin in pH optimum, in some specificity, and considerably in primary structure (Fig.…”

Section: Gastric Proteasesmentioning

confidence: 99%

Evolution in the structure and function of aspartic proteases

Tang

Wong

1987

J of Cellular Biochemistry

290

194

View full text Add to dashboard Cite

show abstract

“…Residues ofPAG that were sequentially homologous to the active site of pepsin were modeled in the context of a porcine pepsin (24), entry 4PEP, obtained from the Protein Data Bank (25). Residues 30-36 and 213-219 of porcine pepsin were replaced with the side chains of residues 72-78 and 255-261 of oPAG and residues 72-78 and 253-259 of bPAG by using PSFRODO (26).…”

mentioning

confidence: 99%

Identification of the major pregnancy-specific antigens of cattle and sheep as inactive members of the aspartic proteinase family.

Xie

Low

Nagel

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

209

206

View full text Add to dashboard Cite

Pregnancy in cattle and sheep can be diagnosed by the presence of a conceptus-derived antigen in maternal serum that is secreted by trophoblast and placental tissue primarily as an acidic component of Mr. 67%000. Molecular doning of its cDNA reveals that the antigen belongs to the aspartic proteinase family and has >50% amino add sequence identity to pepsin, cathepsin D, and cathepsin E. The inferred sequences of the ovine and bovine polypeptides show -73% identity to each other. Critical amino acid substitutions at the active site regions suggest that both proteins are enzymatically inactive. The antigen is a product oftrophoblast binuceate cells that invade maternal endometrium at implantation sites.

show abstract

“…Comprehensive reviews on aspartic proteases have been published [1][2][3]. The threedimensional structure of pepsin [4] and three microbial aspartic proteases including penicillopepsin [5,6], Rhizopus chinensin protease [7] and Endothiaparasitica protease [7] has been reported. The tertiary structures of pepsin and the microbial Correspondence address: L. Polg~ir,…”

mentioning

confidence: 99%

The mechanism of action of aspartic proteases involves ‘push‐pull’ catalysis

Polgár

1987

FEBS Letters

View full text Add to dashboard Cite

In accord with the available kinetic and X-ray crystallographic data, it is proposed that the two catalytically competent carboxyl groups of aspartic proteases constitute a functional unit which mediates the proton from the attacking water molecule to the leaving nitrogen atom of the substrate. Protonation of this nitrogen atom has been the main issue of the previous mechanistic proposals. The first step of the present mechanism involves proton transfer from the water to the aspartic diad and concurrently another proton transfer from the diad to the carbonyl oxygen of the scissile peptide bond. These proton transfers provide the driving force for the bond formation between the substrate and water, which leads to the formation of a tetrahedral intermediate. The intermediate breaks down to products by a similar facilitation, i.e. by concerted general acid-base catalysis, which involves simultaneous proton transfers from the intermediate to the diad and from the diad to the leaving nitrogen of the substrate. The symmetrical mechanism of the formation and decomposition of the tetrahedral adduct resembles that found in the serine protease catalysis.Pepsin; Aspartic protease; Enzyme mechanism Aspartic proteases include several important enzymes, such as pepsin, chymosin, renin, cathepsin D and the proteases isolated from numerous fungi. The amino acid sequences of all these enzymes are homologous, in particular around the active-site residues. Comprehensive reviews on aspartic proteases have been published [1][2][3]. The threedimensional structure of pepsin [4] and three microbial aspartic proteases including penicillopepsin [5,6], Rhizopus chinensin protease [7] and Endothiaparasitica protease [7] has been reported. The tertiary structures of pepsin and the microbial Correspondence address: L. Polg~ir,

show abstract

X-ray diffraction analysis of porcine pepsin structure

Cited by 15 publications

References 0 publications

Evolution in the structure and function of aspartic proteases

Evolution in the structure and function of aspartic proteases

Identification of the major pregnancy-specific antigens of cattle and sheep as inactive members of the aspartic proteinase family.

The mechanism of action of aspartic proteases involves ‘push‐pull’ catalysis

Contact Info

Product

Resources

About