A New Family of Proteinases is Defined by Several Snake Venom Metalloproteinases

Hite, L A; Fox, Jay W.; Bjarnason, Jón B.

doi:10.1515/bchm3.1992.373.2.381

Cited by 35 publications

(19 citation statements)

References 15 publications

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“…the presence of a fifth tyrosine zinc ligand correlates with the absence of a 'cysteine switch region' [28,29] in the proparts of the corresponding metalloproteinases, presumably reflecting unwanted interference of this tyrosine residue with the mercapto-group of a cysteine peptide.…”

Section: Resultsmentioning

confidence: 99%

Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc‐binding environments (HEXXHXXGXXH and Met‐turn) and topologies and should be grouped into a common family, the ‘metzincins’

1993

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The X-ray crystal structures of two zmc endopeptldases. astacin from crayfish. and adamalysm II from snake venom, reveal a strong overall lopologlcal equivalence and virtually Identical extended HEXXHXXGXXH zinc-binding segments, but m addition a methlomne-containing turn of similar conformatlon (the 'Met-turn'). which forms a hydrophobic basis for the zmc ion and the three ligandmg hlstidine residues. These two features are also present in a similar arrangement m the matrix metalloproteinases (matrixins) and in the large bacterial Serratra proteinase-like peptidases (serralysins).We suggest that these four proteinases represent members of distinct subfamilies which can be grouped together in a family, for which we propose the designation, metzmcins.Astacm; Snake venom metalloproteinase; Matrix metalloprotemase; Thermolysm; Zmc endopeptidase family: Protein crystal structure

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Section: Resultsmentioning

confidence: 99%

Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc‐binding environments (HEXXHXXGXXH and Met‐turn) and topologies and should be grouped into a common family, the ‘metzincins’

1993

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“…The primary structures indicated that the venom enzymes belong to a distinct metalloproteinase Family, all of which contain the HEXXH motif, but which have no significant sequence similarity with any other known metalloproteinases except for this region [9]. However, as can be seen from Fig.…”

Section: Familiesmentioning

confidence: 95%

“…Although this motif is well conserved in these en~mes, the third zinc ligand (the remote glutamic acid) is present only in a few clo;,ely related bacterial metalloendopeptidases [6]. However, high homologies in the sequences following the HEXXH motif have been noticed in several groups of metalloproteases, including collagenases, astacin family proteins, and snake venom metalloprotclnases [7][8][9]. The information on the crystal structure of astacin has greatly facilitated identification of additional zinc ligands in thez~ enzymes [4].…”

Section: Introductionmentioning

confidence: 99%

Families of metalloendopeptidases and their relationships

1992

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Crystal structures available for four metalloendopeptidascs have revealed zinc ligands for these enzymes. New sequence information has made it possible to compare the primary structures of the zinc-binding site in metalloendapeptidases. A scheme based on the zinc-bindin8 sit~ is proposed to classify metalloendopeptidases into five distinct families: thermolysin, astacin, serratia, matrixin, and snake venom metalloproteinases. Two histidlnes and one 81utamate are zinc-ligands in the thermolysin family. Three histiciincs and one tyrosine are zinc ligands in the other four families, which are further distinguished by the identity of the residue following the third histidine and by the environment surrounding the tyro~iae.

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“…In the present study, an analysis of the depth or the distance between the S' 1 -pocket and the catalytic site cavity revealed no significant differences or correlation to hemorrhagic activities for the C. s. scutulatus metalloproteinase models. While the atrolysins have been characterized as hemorrhagic toxins that cleave similar substrates in vitro [55,56], the fact that their catalytic clefts superimpose well with each other but poorly to weakly hemorrhagic C. s. scutulatus metalloproteinases is consistent with this observation.…”

Section: Discussionmentioning

confidence: 70%

Molecular models of the Mojave rattlesnake (Crotalus scutulatus scutulatus) venom metalloproteinases reveal a structural basis for differences in hemorrhagic activities

Dagda

Gasanov²,

Zhang³

et al. 2014

J Biol Phys

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Rattlesnake venom can differ in composition and in metalloproteinase-associated activities. The molecular basis for this intra-species variation in Crotalus scutulatus scutulatus (Mojave rattlesnake) remains an enigma. To understand the molecular basis for intra-species variation of metalloproteinase-associated activities, we modeled the threedimensional structures of four metalloproteinases based on the amino acid sequence of four variations of the proteinase domain of the C. s. scutulatus metalloproteinase gene (GP1, GP2, GP3, and GP4). For comparative purposes, we modeled the atrolysin metalloproteinases of C. atrox as well. All molecular models shared the same topology. While the atrolysin metalloproteinase molecular models contained highly conserved substrate binding sites, the Mojave rattlesnake metalloproteinases showed higher structural divergence when superimposed onto each other. The highest structural divergence among the four C. s. scutulatus molecular models was located at the northern cleft wall and the S' 1 -pocket of the substrate binding site, molecular regions that modulate substrate selectivity. Molecular dynamics and field potential maps for each C. s. scutulatus metalloproteinase model demonstrated that the non-hemorrhagic metalloproteinases (GP2 and GP3) contain highly basic molecular and field potential surfaces while the hemorrhagic metalloproteinases GP1 and atrolysin C showed extensive acidic field potential maps and shallow but less dynamic active site pockets. Hence, differences in the spatial arrangement of the northern cleft wall, the S' 1 -pocket, and the physico-chemical environment surrounding the catalytic site contribute to differences in metalloproteinase activities in the Mojave rattlesnake. Our results provide a structural basis for variation of metalloproteinase-associated activities in the rattlesnake venom of the Mojave rattlesnake.

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A New Family of Proteinases is Defined by Several Snake Venom Metalloproteinases

Cited by 35 publications

References 15 publications

Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc‐binding environments (HEXXHXXGXXH and Met‐turn) and topologies and should be grouped into a common family, the ‘metzincins’

Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc‐binding environments (HEXXHXXGXXH and Met‐turn) and topologies and should be grouped into a common family, the ‘metzincins’

Families of metalloendopeptidases and their relationships

Molecular models of the Mojave rattlesnake (Crotalus scutulatus scutulatus) venom metalloproteinases reveal a structural basis for differences in hemorrhagic activities

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