Genomic overview of serine proteases

Yousef, George M.; Kopolovic, Ari D; Elliott, Marc B.; Diamandis, Eleftherios P.

doi:10.1016/s0006-291x(03)00638-7

Cited by 53 publications

(41 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The Ser-His-Asp triad can be replaced with Ser-His-Glu, Ser-His-His or Ser-Lys depending on the family of serine protease [20,21]. The serine proteases are categorized by tertiary structures into the super families of the trypsin-like or subtilisin-like [2,19,20]. Examples of the trypsin-like serine proteases, the larger of the super families, are trypsin, chymotrypsin, thrombin, factor IX a, and factor Xa [2,19,20].…”

Section: Serine Proteasesmentioning

confidence: 99%

“…The serine proteases are categorized by tertiary structures into the super families of the trypsin-like or subtilisin-like [2,19,20]. Examples of the trypsin-like serine proteases, the larger of the super families, are trypsin, chymotrypsin, thrombin, factor IX a, and factor Xa [2,19,20]. Interestingly, some cysteine proteases adopt the trypsin-like structure [22].…”

Section: Serine Proteasesmentioning

confidence: 99%

“…The trypsin-like proteases cleave positively charged residues (Lys or Arg are preferred at P 1 ), elastase-like proteases prefer small hydrophobic residues (Ala or Val are preferred at P 1 ) while chymotrypsin-like proteases prefer large hydrophobic residues (Phe, Tyr, or Leu) [2,19,20].…”

Section: Serine Proteasesmentioning

confidence: 99%

“…While some proteases are nonspecific, others are highly specific both in their substrate selection and cleavage recognition sites. Proteases account for ~2% of the human genome with 553 defined members [1,2] and 1-5% of the genomes in infectious organisms such as bacteria, parasites and viruses [3]. Proteases regulate many cellular processes, such as protein degradation [4,5], digestion [6,7] blood coagulation [8], wound healing [9], ovulation [10], embryonic development [11], bone formation [12], neuronal outgrowth [13], cell-cycle regulation [14], immune and inflammatory response [15], angiogenesis [16] and apoptosis [17].…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, some cysteine proteases adopt the trypsin-like structure [22]. Examples of the subtilisin-like serine proteases are proteinase K and thermitase [2,19,20]. …”

mentioning

confidence: 99%

See 4 more Smart Citations

Proteases: Nature’s Destroyers and the Drugs that Stop Them

Veltri¹

2015

PPIJ

View full text Add to dashboard Cite

Proteases are found in all life forms and regulate many cellular pathways. Proteases have been proven as viable drug targets. This paper reviews the mechanism of hydrolysis of the amino acid based aspartic, cysteine, serine and threonine proteases and will also highlight the current anti protease therapeutics in the clinic. the oxygen of the carbonyl drive the cleavage of the peptide bond, which abstracts hydrogen from the general base. Water then releases the second half of the product from the active site residue. The oxyanion hole generated during the transition state is stabilized through hydrogen bonding with amino groups of the backbone. The role of the oxyanion hole is not fully understood [18]. While the chemistry of the mechanism of hydrolysis is similar for serine, aspartic, cysteine and threonine proteases, the amino acids involved in catalysis are what define the various classes. The different classes of proteases are discussed below. Serine ProteasesSerine proteases [19][20][21] use an active site serine to hydrolyze a peptide bond. The other amino acids involved in catalysis vary between the different serine protease groups. The Ser-His-Asp triad can be replaced with Ser-His-Glu, Ser-His-His or Ser-Lys depending on the family of serine protease [20,21]. The serine proteases are categorized by tertiary structures into the super families of the trypsin-like or subtilisin-like [2,19,20]. Examples of the trypsin-like serine proteases, the larger of the super families, are trypsin, chymotrypsin, thrombin, factor IX a, and factor Xa [2,19,20]. Interestingly, some cysteine proteases adopt the trypsin-like structure [22]. Examples of the subtilisin-like serine proteases are proteinase K and thermitase [2,19,20]. Proteases: Nature's Destroyers and the Drugs that Stop Them 3/11Copyright: ©2015 Veltri Citation: Veltri CA (2015) Proteases: Nature's Destroyers and the Drugs that Stop Them. Pharm Pharmacol Int J 2(6): 00044. DOI: 10.15406/ ppij.2015.02.00044Along with tertiary structure, serine proteases are designed against the nature of the P 1 residue recognized by the protease types. The trypsin-like proteases cleave positively charged residues (Lys or Arg are preferred at P 1 ), elastase-like proteases prefer small hydrophobic residues (Ala or Val are preferred at P 1 ) while chymotrypsin-like proteases prefer large hydrophobic residues (Phe, Tyr, or Leu) [2,19,20]. Aspartic ProteasesAspartic proteases [19,[23][24][25][26] use two aspartic acid residues to hydrolyze a peptide bond. These proteases are categorized into the super families of pepsin-like or viral retropepsin-like due to the tertiary structure [23,24,26,27]. The pepsin-like include pepsin, cathepsin D and chymosin [23,27]. The viral retropepsinlike include the retro pepsins of the immune viruses HIV, FIV and SIV [24,26].Aspartic proteases are unique in the fact they do not have a His residue in their active site. The general acid-base mechanism proposed for peptide hydrolysis involves two Asp residues and uses water to attack the targe...

show abstract

Section: Serine Proteasesmentioning

confidence: 99%

Section: Serine Proteasesmentioning

confidence: 99%

Section: Serine Proteasesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Interestingly, some cysteine proteases adopt the trypsin-like structure [22]. Examples of the subtilisin-like serine proteases are proteinase K and thermitase [2,19,20]. …”

mentioning

confidence: 99%

See 3 more Smart Citations

Proteases: Nature’s Destroyers and the Drugs that Stop Them

Veltri¹

2015

PPIJ

View full text Add to dashboard Cite

show abstract

Serine protease identification (in vitro) and molecular structure predictions (in silico) from a phytopathogenic fungus,Alternaria solani

Chandrasekaran

Chandrasekar

et al. 2013

J. Basic Microbiol.

View full text Add to dashboard Cite

Serine proteases are involved in an enormous number of biological processes. The present study aims at characterizing three‐dimensional (3D) molecular architecture of serine proteases from early blight pathogen, Alternaria solani that are hypothesized to be markers of phytopathogenicity. A serine protease was purified to homogeneity and MALDI‐TOF‐MS/MS analysis revealed that protease produced by A. solani belongs to alkaline serine proteases (AsP). AsP is made up of 403 amino acid residues with molecular weight of 42.1 kDa (Isoelectric point – 6.51) and its molecular formula was C1859H2930N516O595S4. AsP structure model was built based on its comparative homology with serine protease using the program, MODELER. AsP had 16 β‐sheets and 10 α‐helices, with Ser350 (G347–G357), Asp158 (D158–H169), and His193 (H193–G203) in separate turn/coil structures. Biological metal binding region situated near 6th‐helix and His193 residue is responsible for metal binding site. Also, calcium ion (Ca2+) is coordinated by the carboxyl groups of Lys84, Ile85, Lys86, Asp87, Phe88, Ala89, Ala90 (K84–A90) for first Ca2+ binding site and carbonyl oxygen atom of Lys244, Gly245, Arg246, Thr247, Lys248, Lys249, and Ala250 (K244–A250), for second Ca2+ binding site. Moreover, Ramachandran plot analysis of protein residues falling into most favored secondary structures were determined (83.3%). The predicted molecular 3D structural model was further verified using PROCHECK, ERRAT, and VADAR servers to confirm the geometry and stereo‐chemical parameters of the molecular structural design. The functional analysis of AsP 3D molecular structure predictions familiar in the current study may provide a new perspective in the understanding and identification of antifungal protease inhibitor designing.

show abstract