Alignment/Phylogeny of the Papain Superfamily of Cysteine Proteases

Berti, Paul J.; Storer, Andrew C.

doi:10.1006/jmbi.1994.0083

Cited by 367 publications

(281 citation statements)

References 0 publications

Supporting

Mentioning

270

Contrasting

Unclassified

Order By: Relevance

“…3 and 4) can be considered as an "electrostatic fingerprint" representative of the papain family of cysteine proteinases (and possibly for the superfamily). This conclusion is based on the analysis of the work of Berti and Storer, 3 where an alignment/phylogeny study of cysteine proteases belonging to the papain superfamily is presented. The nine residues close to the active site responsible for the basic characteristics of the papain electrostatic profile are located at structurally conserved regions (SCRs) and, with the exception of Asp158, these residues are highly conserved (or substituted by residues with equivalent characteristics) in the cysteine proteases sequences.…”

Section: The Net Electric Field Highly Aligned In the (Cys25)-sg3(hismentioning

confidence: 99%

“…This enzyme has a large degree of similarity, [1][2][3] in both structure and enzymatic properties, with a number of plant (e.g., caricain, a papain variant from Carica papaya; actinidin from Actinidia chinensis; ficin from Ficus glabrata), mammalian lysosomal (e.g., cathepsins B, H, L, S), and parasite proteases (e.g., cruzipain from the protozoa Trypanosoma cruzi, falcipain from the protozoa Plasmodium falciparum). Members of the papain family are implicated in a variety of physiologic and pathologic processes in eukaryotic organisms and are considered as important molecular targets in the development of chemotherapy against parasitic diseases (e.g., Chagas' disease, malaria) that affect millions of people around the world.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Electrostatic properties in the catalytic site of papain: A possible regulatory mechanism for the reactivity of the ion pair

et al. 2003

View full text Add to dashboard Cite

We present an analysis of the electrostatic properties in the catalytic site of papain (EC 3.4.22.2), an archetype enzyme of the C1 cysteine proteinase family, and we investigate their possible role in the formation, stabilization and regulation of the Cys25 (؊) …His159 (؉) catalytic ion pair. The electrostatic properties were computed using a reassociation method based in multicentered multipolar expansions obtained from ab initio quantum calculations of overlapping protein fragments. Solvent effects were introduced by coupling the use of multicentered multipolar expansions to two continuum boundary element methods to solve the Poisson and the linearized Poisson-Boltzmann equations. The electrostatic profile found in the proton transfer region of papain showed that this enzyme has a well-defined electrostatic environment to favor the formation and stabilization of the catalytic ion pair. The papain catalytic site electrostatic profile can be considered as an electrostatic fingerprint of the papain family with the following characteristics: (i) the presence of a net electric field highly aligned in the (Cys25)-SG3(His159)-ND1 direction; (ii) the electrostatic profile has a saddlepoint character; (iii) it is basically a local environmental effect. Furthermore, our analysis describes a possible regulatory mechanism (the E SG3 ND1 attenuation effect) controlling the ion pair reactivity and permits to infer the Asp57 acidic residue as the most probable candidate to act as the electrostatic modulator. Proteins 2003;52:236 -253.

show abstract

Section: The Net Electric Field Highly Aligned In the (Cys25)-sg3(hismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Electrostatic properties in the catalytic site of papain: A possible regulatory mechanism for the reactivity of the ion pair

et al. 2003

View full text Add to dashboard Cite

show abstract

“…They also share papain-family sequence motifs, but, as noted previously for SERA [16,17], the active site cysteine (Cys 25 in the papain numbering system) is replaced by a serine, and, in most cases, the active site histidine (His 159 ) is replaced by leucine or methionine. The three other papain family active site residues, Gln 19 , Asn 175 and Trp 177 [18], are conserved in SERA and all described SERA homologues. The SERPH subclass is represented by SERPH, the newly identified P. 6i6ax homologue SERPH vivax , and two P. 6inckei homologues SERA vinckei -1 and SERA vinckei -2 (Fig.…”

mentioning

confidence: 97%

“…Compared to the SERA subclass, SERPHsubclass proteins share greater ( 70%) amino acid identity within the protease domain, and they uniformly have conservation of papain family active site amino acids. Considering the 21 amino acids that are conserved in ] 95% of 82 evaluated papain-family proteases [19], identity with papain Alignment of the protease domains of SERPH and closely related homologues from P. 6i6ax (SERPH vivax ) and P. 6inckei (SERA vinckei -1 and SERA vinckei -2). Numbering is for SERPH.…”

mentioning

confidence: 99%

“…Papain-family active site amino acids [18] are marked by arrows. Amino acids that are conserved between papain and ] 95% of 82 evaluated papain family proteases [19] are shown above the aligned sequences, and amino acids that conform to the papain sequence at these sites are underlined. Blood was collected from P. 6inckei-infected mice and schizont-infected erythrocytes were isolated with a Percoll gradient [21].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Plasmodial serine repeat antigen homologues with properties of schizont cysteine proteases

Gor

Wiser

et al. 1998

Molecular and Biochemical Parasitology

View full text Add to dashboard Cite

Proteases appear to be required for critical events in the erythrocytic life cycle of malaria parasites, including the rupture of erythrocytes by mature schizonts and the subsequent invasion of erythrocytes by daughter merozoites [1,2]. This conclusion is supported by studies showing that parasite rupture and invasion of erythrocytes are inhibited by serine and cysteine protease inhibitors [1] and that the proteolytic processing of late schizont-stage proteins is required for the completion of the erythrocytic cycle [3,4]. A number of schizont protease activities have been identified biochemically [2], but limitations on available quantities of protein have made it difficult to definitively characterize these proteases or to ascertain their specific biological roles.The Plasmodium falciparum serine repeat antigen (known as SERA, SERA-1, SERP or P126 [5][6][7]) is being studied as a potential vaccine component [8]. A number of SERA homologues have been described, namely serine repeat protein homologue (SERPH [9] or SERA-2 [10]) and SERA-3 [10] from P. falciparum and five homologues from Plasmodium 6i6ax [11]. SERA and SERPH have been localized to the parasitophorous vacuole of mature schizonts [9,12], and SERA fragments are released into the bloodstream near the time of erythrocyte rupture [12]. SERA and its homologues all contain a 30 kDa 'protease domain' that has similarity in sequence to papain-family cysteine proteases, particularly near highly conserved active site residues [13] (Fig. 1A). Taken together, available data suggest that SERA and SERPH may act as late schizontAbbre6iations: SERA, serine repeat antigen; SERPH, serine repeat antigen homologue.

show abstract

Bleomycin Hydrolase

Montoya¹,

Lazo²

2002

Wiley Encyclopedia of Molecular Medicine

View full text Add to dashboard Cite

Alignment/Phylogeny of the Papain Superfamily of Cysteine Proteases

Cited by 367 publications

References 0 publications

Electrostatic properties in the catalytic site of papain: A possible regulatory mechanism for the reactivity of the ion pair

Electrostatic properties in the catalytic site of papain: A possible regulatory mechanism for the reactivity of the ion pair

Plasmodial serine repeat antigen homologues with properties of schizont cysteine proteases

Bleomycin Hydrolase

Contact Info

Product

Resources

About