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Proteolysis

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Thehydrolysisof aprotein(red) by thenucleophilic attackof water (blue). The uncatalysed half-life is several hundred years.

Proteolysisis the breakdown ofproteinsinto smallerpolypeptidesoramino acids.Uncatalysed, thehydrolysisofpeptide bondsis extremely slow, taking hundreds of years. Proteolysis is typicallycatalysedby cellularenzymescalledproteases,but may also occur by intra-molecular digestion.

Proteolysis in organisms serves many purposes; for example,digestive enzymesbreak down proteins in food to provide amino acids for the organism, while proteolytic processing of a polypeptide chain after its synthesis may be necessary for the production of an active protein. It is also important in the regulation of some physiological and cellular processes includingapoptosis,as well as preventing the accumulation of unwanted or misfolded proteins in cells. Consequently, abnormality in the regulation of proteolysis can cause disease.

Proteolysis can also be used as an analytical tool for studying proteins in the laboratory, and it may also be used in industry, for example in food processing and stain removal.

Biological functions[edit]

Post-translational proteolytic processing[edit]

Limited proteolysis of a polypeptide during or aftertranslationinprotein synthesisoften occurs for many proteins. This may involve removal of theN-terminalmethionine,signal peptide,and/or the conversion of an inactive or non-functional protein to an active one. The precursor to the final functional form of protein is termedproprotein,and these proproteins may be first synthesized as preproprotein. For example,albuminis first synthesized as preproalbumin and contains an uncleaved signal peptide. This forms the proalbumin after the signal peptide is cleaved, and a further processing to remove the N-terminal 6-residue propeptide yields the mature form of the protein.[1]

Removal of N-terminal methionine[edit]

The initiating methionine (and, in prokaryotes,fMet) may be removed during translation of the nascent protein. ForE. coli,fMet is efficiently removed if the second residue is small and uncharged, but not if the second residue is bulky and charged.[2]In bothprokaryotesandeukaryotes,the exposed N-terminal residue may determine the half-life of the protein according to theN-end rule.

Removal of the signal sequence[edit]

Proteins that are to be targeted to a particular organelle or for secretion have an N-terminalsignal peptidethat directs the protein to its final destination. This signal peptide is removed by proteolysis after their transport through amembrane.

Cleavage of polyproteins[edit]

Some proteins and most eukaryotic polypeptide hormones are synthesized as a large precursor polypeptide known as a polyprotein that requires proteolytic cleavage into individual smaller polypeptide chains. The polyproteinpro-opiomelanocortin(POMC) contains many polypeptide hormones. The cleavage pattern of POMC, however, may vary between different tissues, yielding different sets of polypeptide hormones from the same polyprotein.

Manyvirusesalso produce their proteins initially as a single polypeptide chain that were translated from apolycistronicmRNA. This polypeptide is subsequently cleaved into individual polypeptide chains.[1]Common names for the polyprotein includegag(group-specific antigen) inretrovirusesandORF1abinNidovirales.The latter name refers to the fact that aslippery sequencein the mRNA that codes for the polypeptide causesribosomal frameshifting,leading to two different lengths of peptidic chains (aandab) at an approximately fixed ratio.

Cleavage of precursor proteins[edit]

Many proteins and hormones are synthesized in the form of their precursors -zymogens,proenzymes,andprehormones.These proteins are cleaved to form their final active structures.Insulin,for example, is synthesized aspreproinsulin,which yieldsproinsulinafter the signal peptide has been cleaved. The proinsulin is then cleaved at two positions to yield two polypeptide chains linked by twodisulfide bonds.Removal of two C-terminal residues from the B-chain then yields the mature insulin.Protein foldingoccurs in the single-chain proinsulin form which facilitates formation of the ultimate inter-peptide disulfide bonds, and the ultimate intra-peptide disulfide bond, found in the native structure of insulin.

Proteases in particular are synthesized in the inactive form so that they may be safely stored in cells, and ready for release in sufficient quantity when required. This is to ensure that the protease is activated only in the correct location or context, as inappropriate activation of these proteases can be very destructive for an organism. Proteolysis of the zymogen yields an active protein; for example, whentrypsinogenis cleaved to formtrypsin,a slight rearrangement of the protein structure that completes the active site of the protease occurs, thereby activating the protein.

Proteolysis can, therefore, be a method of regulating biological processes by turning inactive proteins into active ones. A good example is theblood clotting cascadewhereby an initial event triggers a cascade of sequential proteolytic activation of many specific proteases, resulting in blood coagulation. Thecomplement systemof theimmune responsealso involves a complex sequential proteolytic activation and interaction that result in an attack on invading pathogens.

Protein degradation[edit]

Protein degradation may take place intracellularly or extracellularly. In digestion of food, digestive enzymes may be released into the environment forextracellular digestionwhereby proteolytic cleavage breaks proteins into smaller peptides and amino acids so that they may be absorbed and used. In animals the food may be processed extracellularly in specializedorgansorguts,but in many bacteria the food may be internalized viaphagocytosis.Microbial degradation of protein in the environment can be regulated by nutrient availability. For example, limitation for major elements in proteins (carbon, nitrogen, and sulfur) induces proteolytic activity in the fungusNeurospora crassa[3]as well as in of soil organism communities.[4]

Proteins in cells are broken into amino acids. This intracellular degradation of protein serves multiple functions: It removes damaged and abnormal proteins and prevents their accumulation. It also serves to regulate cellular processes by removing enzymes and regulatory proteins that are no longer needed. The amino acids may then be reused for protein synthesis.

Lysosome and proteasome[edit]

Structure of a proteasome. Its active sites are inside the tube (blue) where proteins are degraded.

The intracellular degradation of protein may be achieved in two ways—proteolysis inlysosome,or aubiquitin-dependent process that targets unwanted proteins toproteasome.Theautophagy-lysosomal pathway is normally a non-selective process, but it may become selective upon starvation whereby proteins with peptide sequence KFERQ or similar are selectively broken down. The lysosome contains a large number of proteases such ascathepsins.

The ubiquitin-mediated process is selective. Proteins marked for degradation are covalently linked to ubiquitin. Many molecules of ubiquitin may be linked in tandem to a protein destined for degradation. The polyubiquinated protein is targeted to an ATP-dependent protease complex, the proteasome. The ubiquitin is released and reused, while the targeted protein is degraded.

Rate of intracellular protein degradation[edit]

Different proteins are degraded at different rates. Abnormal proteins are quickly degraded, whereas the rate of degradation of normal proteins may vary widely depending on their functions. Enzymes at important metabolic control points may be degraded much faster than those enzymes whose activity is largely constant under all physiological conditions. One of the most rapidly degraded proteins isornithine decarboxylase,which has a half-life of 11 minutes. In contrast, other proteins likeactinandmyosinhave a half-life of a month or more, while, in essence,haemoglobinlasts for the entire life-time of anerythrocyte.[5]

TheN-end rulemay partially determine the half-life of a protein, and proteins with segments rich inproline,glutamic acid,serine,andthreonine(the so-calledPEST proteins) have short half-life.[6]Other factors suspected to affect degradation rate include the rate deamination of glutamine andasparagineand oxidation ofcystein,histidine,and methionine, the absence of stabilizing ligands, the presence of attached carbohydrate or phosphate groups, the presence of free α-amino group, the negative charge of protein, and the flexibility and stability of the protein.[5]Proteins with larger degrees ofintrinsic disorderalso tend to have short cellular half-life,[7]with disordered segments having been proposed to facilitate efficient initiation of degradation by theproteasome.[8][9]

The rate of proteolysis may also depend on the physiological state of the organism, such as its hormonal state as well as nutritional status. In time of starvation, the rate of protein degradation increases.

Digestion[edit]

In humandigestion,proteins in food are broken down into smaller peptide chains bydigestive enzymessuch aspepsin,trypsin,chymotrypsin,andelastase,and into amino acids by various enzymes such ascarboxypeptidase,aminopeptidase,anddipeptidase.It is necessary to break down proteins into small peptides (tripeptides and dipeptides) and amino acids so they can be absorbed by the intestines, and the absorbed tripeptides and dipeptides are also further broken into amino acids intracellularly before they enter the bloodstream.[10]Different enzymes have different specificity for their substrate; trypsin, for example, cleaves the peptide bond after a positively charged residue (arginineandlysine); chymotrypsin cleaves the bond after an aromatic residue (phenylalanine,tyrosine,andtryptophan); elastase cleaves the bond after a small non-polar residue such as alanine or glycine.

In order to prevent inappropriate or premature activation of the digestive enzymes (they may, for example, trigger pancreatic self-digestion causingpancreatitis), these enzymes are secreted as inactive zymogen. The precursor ofpepsin,pepsinogen,is secreted by the stomach, and is activated only in the acidic environment found in stomach. Thepancreassecretes the precursors of a number of proteases such astrypsinandchymotrypsin.The zymogen of trypsin istrypsinogen,which is activated by a very specific protease,enterokinase,secreted by themucosaof theduodenum.The trypsin, once activated, can also cleave other trypsinogens as well as the precursors of other proteases such as chymotrypsin and carboxypeptidase to activate them.

In bacteria, a similar strategy of employing an inactive zymogen or prezymogen is used.Subtilisin,which is produced byBacillus subtilis,is produced as preprosubtilisin, and is released only if the signal peptide is cleaved and autocatalytic proteolytic activation has occurred.

Cellular regulation[edit]

Proteolysis is also involved in the regulation of many cellular processes by activating or deactivating enzymes, transcription factors, and receptors, for example in the biosynthesis of cholesterol,[11]or the mediation of thrombin signalling throughprotease-activated receptors.[12]

Some enzymes at important metabolic control points such as ornithine decarboxylase is regulated entirely by its rate of synthesis and its rate of degradation. Other rapidly degraded proteins include the protein products of proto-oncogenes, which play central roles in the regulation of cell growth.

Cell cycle regulation[edit]

Cyclinsare a group of proteins that activatekinasesinvolved in cell division. The degradation of cyclins is the key step that governs the exit frommitosisand progress into the nextcell cycle.[13]Cyclins accumulate in the course the cell cycle, then abruptly disappear just before theanaphaseof mitosis. The cyclins are removed via a ubiquitin-mediated proteolytic pathway.

Apoptosis[edit]

Caspasesare an important group of proteases involved inapoptosisorprogrammed cell death.The precursors of caspase, procaspase, may be activated by proteolysis through its association with a protein complex that formsapoptosome,or bygranzyme B,or via thedeath receptorpathways.

Autoproteolysis[edit]

Autoproteolysis takes place in some proteins, whereby thepeptide bondis cleaved in a self-catalyzedintramolecular reaction.Unlikezymogens,these autoproteolytic proteins participate in a "single turnover" reaction and do not catalyze further reactions post-cleavage. Examples include cleavage of the Asp-Pro bond in a subset ofvon Willebrand factortype D (VWD) domains[14][15]andNeisseria meningitidisFrpC self-processing domain,[16]cleavage of the Asn-Pro bond inSalmonellaFlhB protein,[17]YersiniaYscU protein,[18]as well as cleavage of the Gly-Ser bond in a subset of sea urchin sperm protein, enterokinase, and agrin (SEA) domains.[19]In some cases, the autoproteolytic cleavage is promoted by conformational strain of the peptide bond.[19]

Proteolysis and diseases[edit]

Abnormal proteolytic activity is associated with many diseases.[20]Inpancreatitis,leakage of proteases and their premature activation in the pancreas results in the self-digestion of thepancreas.People withdiabetes mellitusmay have increased lysosomal activity and the degradation of some proteins can increase significantly. Chronic inflammatory diseases such asrheumatoid arthritismay involve the release of lysosomal enzymes into extracellular space that break down surrounding tissues. Abnormal proteolysis may result in many age-related neurological diseases such asAlzheimer's due to generation and ineffective removal of peptides that aggregate in cells.[21]

Proteases may be regulated byantiproteasesorprotease inhibitors,and imbalance between proteases and antiproteases can result in diseases, for example, in the destruction of lung tissues inemphysemabrought on bysmokingtobacco. Smoking is thought to increase theneutrophilsandmacrophagesin the lung which release excessive amount of proteolytic enzymes such aselastase,such that they can no longer be inhibited byserpinssuch asα1-antitrypsin,thereby resulting in the breaking down of connective tissues in the lung. Other proteases and their inhibitors may also be involved in this disease, for examplematrix metalloproteinases(MMPs) andtissue inhibitors of metalloproteinases(TIMPs).[22]

Other diseases linked to aberrant proteolysis includemuscular dystrophy,degenerative skin disorders, respiratory and gastrointestinal diseases, andmalignancy.

Non-enzymatic processes[edit]

Protein backbones are very stable in water at neutral pH and room temperature, although the rate of hydrolysis of different peptide bonds can vary. The half life of a peptide bond under normal conditions can range from 7 years to 350 years, even higher for peptides protected by modified terminus or within the protein interior.[23][24][25]The rate of hydrolysis however can be significantly increased by extremes of pH and heat. Spontaneous cleavage of proteins may also involve catalysis by zinc on serine and threonine.[26]

Strongmineral acidscan readily hydrolyse the peptide bonds in a protein (acid hydrolysis). The standard way to hydrolyze a protein or peptide into its constituent amino acids for analysis is to heat it to 105 °C for around 24 hours in 6Mhydrochloric acid.[27]However, some proteins are resistant to acid hydrolysis. One well-known example isribonuclease A,which can be purified by treating crude extracts with hotsulfuric acidso that other proteins become degraded while ribonuclease A is left intact.[28]

Certain chemicals cause proteolysis only after specific residues, and these can be used to selectively break down a protein into smaller polypeptides for laboratory analysis.[29]For example,cyanogen bromidecleaves the peptide bond after amethionine.Similar methods may be used to specifically cleavetryptophanyl,aspartyl,cysteinyl,andasparaginylpeptide bonds. Acids such astrifluoroacetic acidandformic acidmay be used for cleavage.

Like other biomolecules, proteins can also be broken down by high heat alone. At 250 °C, the peptide bond may be easily hydrolyzed, with its half-life dropping to about a minute.[27][30]Protein may also be broken down without hydrolysis throughpyrolysis;smallheterocyclic compoundsmay start to form upon degradation. Above 500 °C,polycyclic aromatic hydrocarbonsmay also form,[31][32]which is of interest in the study of generation ofcarcinogensin tobacco smoke and cooking at high heat.[33][34]

Laboratory applications[edit]

Proteolysis is also used in research and diagnostic applications:

Protease enzymes[edit]

Main article:Protease

Proteases may be classified according to the catalytic group involved in its active site.[39]

Venoms[edit]

Certain types of venom, such as those produced by venomoussnakes,can also cause proteolysis. These venoms are, in fact, complex digestive fluids that begin their work outside of the body. Proteolytic venoms cause a wide range of toxic effects,[40]including effects that are:

See also[edit]

References[edit]

  1. ^abThomas E Creighton (1993).Proteins: Structures and Molecular Properties(2nd ed.). W H Freeman and Company. pp.78–86.ISBN978-0-7167-2317-2.
  2. ^P H Hirel; M J Schmitter; P Dessen; G Fayat; S Blanquet (1989)."Extent of N-terminal methionine excision from Escherichia coli proteins is governed by the side-chain length of the penultimate amino acid".Proc Natl Acad Sci U S A.86(21): 8247–51.Bibcode:1989PNAS...86.8247H.doi:10.1073/pnas.86.21.8247.PMC298257.PMID2682640.
  3. ^Hanson, M.A., Marzluf, G.A., 1975. Control of the synthesis of a single enzyme by multiple regulatory circuits in Neurospora crassa. Proc. Natl. Acad. Sci. U.S.A. 72, 1240–1244.
  4. ^Sims, G. K., and M. M. Wander. 2002. Proteolytic activity under nitrogen or sulfur limitation. Appl. Soil Ecol. 568:1-5.
  5. ^abThomas E Creighton (1993)."Chapter 10 - Degradation".Proteins: Structures and Molecular Properties(2nd ed.). W H Freeman and Company. pp.463–473.ISBN978-0-7167-2317-2.
  6. ^Voet & Voet (1995).Biochemistry(2nd ed.). John Wiley & Sons. pp.1010–1014.ISBN978-0-471-58651-7.
  7. ^Tompa, P.; Prilusky, J.; Silman, I.; Sussman, J. L. (2008-05-01). "Structural disorder serves as a weak signal for intracellular protein degradation".Proteins.71(2): 903–909.doi:10.1002/prot.21773.ISSN1097-0134.PMID18004785.S2CID13942948.
  8. ^Inobe, Tomonao; Matouschek, Andreas (2014-02-01)."Paradigms of protein degradation by the proteasome".Current Opinion in Structural Biology.24:156–164.doi:10.1016/j.sbi.2014.02.002.ISSN1879-033X.PMC4010099.PMID24632559.
  9. ^van der Lee, Robin; Lang, Benjamin; Kruse, Kai; Gsponer, Jörg; Sánchez de Groot, Natalia; Huynen, Martijn A.; Matouschek, Andreas; Fuxreiter, Monika; Babu, M. Madan (25 September 2014)."Intrinsically Disordered Segments Affect Protein Half-Life in the Cell and during Evolution".Cell Reports.8(6): 1832–1844.doi:10.1016/j.celrep.2014.07.055.ISSN2211-1247.PMC4358326.PMID25220455.
  10. ^Silk DB (1974)."Progress report. Peptide absorption in man".Gut.15(6): 494–501.doi:10.1136/gut.15.6.494.PMC1413009.PMID4604970.
  11. ^Michael S. Brown; Joseph L. Goldstein (May 1997)."The SREBP Pathway: Regulation of Cholesterol Metabolism by Proteolysis of a Membrane-Bound Transcription Factor".Cell.89(3): 331–340.doi:10.1016/S0092-8674(00)80213-5.PMID9150132.S2CID17882616.
  12. ^Shaun R. Coughlin (2000). "Thrombin signalling and protease-activated receptors".Nature.407(6801): 258–264.doi:10.1038/35025229.PMID11001069.S2CID4429634.
  13. ^Glotzer M, Murray AW, Kirschner MW (1991). "Cyclin is degraded by the ubiquitin pathway".Nature.349(6305): 132–8.Bibcode:1991Natur.349..132G.doi:10.1038/349132a0.PMID1846030.S2CID205003883.
  14. ^Lidell, Martin E.; Johansson, Malin E. V.; Hansson, Gunnar C. (2003-04-18)."An autocatalytic cleavage in the C terminus of the human MUC2 mucin occurs at the low pH of the late secretory pathway".The Journal of Biological Chemistry.278(16): 13944–13951.doi:10.1074/jbc.M210069200.ISSN0021-9258.PMID12582180.
  15. ^Bi, Ming; Hickox, John R; Winfrey, Virginia P; Olson, Gary E; Hardy, Daniel M (2003-10-15)."Processing, localization and binding activity of zonadhesin suggest a function in sperm adhesion to the zona pellucida during exocytosis of the acrosome".Biochemical Journal.375(Pt 2): 477–488.doi:10.1042/BJ20030753.ISSN0264-6021.PMC1223699.PMID12882646.
  16. ^Sadilkova, Lenka; Osicka, Radim; Sulc, Miroslav; Linhartova, Irena; Novak, Petr; Sebo, Peter (October 2008)."Single-step affinity purification of recombinant proteins using a self-excising module from Neisseria meningitidis FrpC".Protein Science.17(10): 1834–1843.doi:10.1110/ps.035733.108.PMC2548358.PMID18662906.
  17. ^Minamino, Tohru; Macnab, Robert M. (2000-09-01)."Domain Structure of Salmonella FlhB, a Flagellar Export Component Responsible for Substrate Specificity Switching".Journal of Bacteriology.182(17): 4906–4914.doi:10.1128/JB.182.17.4906-4914.2000.ISSN1098-5530.PMC111371.PMID10940035.
  18. ^Björnfot, Ann-Catrin; Lavander, Moa; Forsberg, Åke; Wolf-Watz, Hans (2009-07-01)."Autoproteolysis of YscU of Yersinia pseudotuberculosis Is Important for Regulation of Expression and Secretion of Yop Proteins".Journal of Bacteriology.191(13): 4259–4267.doi:10.1128/JB.01730-08.ISSN0021-9193.PMC2698497.PMID19395493.
  19. ^abJohansson, Denny G. A.; Macao, Bertil; Sandberg, Anders; Härd, Torleif (2008-04-04). "SEA domain autoproteolysis accelerated by conformational strain: mechanistic aspects".Journal of Molecular Biology.377(4): 1130–1143.doi:10.1016/j.jmb.2008.01.050.ISSN1089-8638.PMID18314133.
  20. ^Kathleen M. Sakamoto (2002)."Ubiquitin-dependent proteolysis: its role in human diseases and the design of therapeutic strategies"(PDF).Molecular Genetics and Metabolism.77(1–2): 44–56.doi:10.1016/S1096-7192(02)00146-4.PMID12359129.
  21. ^De Strooper B. (2010). "Proteases and proteolysis in Alzheimer disease: a multifactorial view on the disease process".Physiological Reviews.90(2): 465–94.doi:10.1152/physrev.00023.2009.PMID20393191.
  22. ^Abboud RT1, Vimalanathan S (2008). "Pathogenesis of COPD. Part I. The role of protease-antiprotease imbalance in emphysema".International Journal of Tuberculosis and Lung Disease.12(4): 361–7.PMID18371259.{{cite journal}}:CS1 maint: numeric names: authors list (link)
  23. ^Daniel. Kahne; W. Clark Still (1988). "Hydrolysis of a peptide bond in neutral water".J. Am. Chem. Soc.110(22): 7529–7534.doi:10.1021/ja00230a041.
  24. ^Radzicka, Anna; Wolfenden, Richard (January 1996). "Rates of Uncatalyzed Peptide Bond Hydrolysis in Neutral Solution and the Transition State Affinities of Proteases".Journal of the American Chemical Society.118(26): 6105–6109.doi:10.1021/ja954077c.
  25. ^Bernard Testa; Joachim M. Mayer (1 July 2003).Hydrolysis in Drug and Prodrug Metabolism.Wiley VCH. pp. 270–288.ISBN978-3-906390-25-3.
  26. ^Brian Lyons; Ann H. Kwan; Roger J.W. Truscott (April 2016)."Spontaneous cleavage of proteins at serine and threonine is facilitated by zinc".Aging Cell.15(2): 237–244.doi:10.1111/acel.12428.PMC4783340.PMID26751411.
  27. ^abThomas E Creighton (1993).Proteins: Structures and Molecular Properties(2nd ed.). W H Freeman and Company. p.6.ISBN978-0-7167-2317-2.
  28. ^"Ribonuclease A".Protein Data Bank.
  29. ^Bryan John Smith (2002). "Chapter 71-75". In John M. Walker (ed.).The Protein Protocols Handbook(2 ed.). Humana Press. pp.485–510.doi:10.1385/1592591698.ISBN978-0-89603-940-7.S2CID3692961.
  30. ^White RH (1984). "Hydrolytic stability of biomolecules at high temperatures and its implication for life at 250 degrees C".Nature.310(5976): 430–2.doi:10.1038/310430a0.PMID6462230.S2CID4315057.
  31. ^Ramesh K. Sharmaa; W.Geoffrey Chana; Jeffrey I. Seemanb; Mohammad R. Hajaligola (January 2003). "Formation of low molecular weight heterocycles and polycyclic aromatic compounds (PACs) in the pyrolysis of α-amino acids".Journal of Analytical and Applied Pyrolysis.66(1–2): 97–121.doi:10.1016/S0165-2370(02)00108-0.
  32. ^Fabbri D, Adamiano A, Torri C (2010). "GC-MS determination of polycyclic aromatic hydrocarbons evolved from pyrolysis of biomass".Anal Bioanal Chem.397(1): 309–17.doi:10.1007/s00216-010-3563-5.PMID20213167.S2CID33835929.
  33. ^White JL, Conner BT, Perfetti TA, Bombick BR, Avalos JT, Fowler KW, Smith CJ, Doolittle DJ (May 2001). "Effect of pyrolysis temperature on the mutagenicity of tobacco smoke condensate".Food Chem Toxicol.39(5): 499–505.doi:10.1016/s0278-6915(00)00155-1.PMID11313117.
  34. ^"Chemicals in Meat Cooked at High Temperatures and Cancer Risk".National Cancer Institute.2 April 2018.
  35. ^Hilz H, Wiegers U, Adamietz P (1975)."Stimulation of Proteinase K action by denaturing agents: application to the isolation of nucleic acids and the degradation of 'masked' proteins".European Journal of Biochemistry.56(1): 103–108.doi:10.1111/j.1432-1033.1975.tb02211.x.PMID1236799.
  36. ^Klenow H, Henningsen I (1970)."Selective Elimination of the Exonuclease Activity of the Deoxyribonucleic Acid Polymerase from Escherichia coli B by Limited Proteolysis".Proc. Natl. Acad. Sci. USA.65(1): 168–175.Bibcode:1970PNAS...65..168K.doi:10.1073/pnas.65.1.168.PMC286206.PMID4905667.
  37. ^Minde DP; Maurice, Madelon M.; Rüdiger, Stefan G. D. (2012). Uversky, Vladimir N (ed.)."Determining biophysical protein stability in lysates by a fast proteolysis assay, FASTpp".PLOS ONE.7(10): e46147.Bibcode:2012PLoSO...746147M.doi:10.1371/journal.pone.0046147.PMC3463568.PMID23056252.
  38. ^Wernimont, A; Edwards, A (2009). Song, Haiwei (ed.)."In situ proteolysis to generate crystals for structure determination: An update".PLOS ONE.4(4): e5094.Bibcode:2009PLoSO...4.5094W.doi:10.1371/journal.pone.0005094.PMC2661377.PMID19352432.
  39. ^Kohei Oda (2012)."New families of carboxyl peptidases: serine-carboxyl peptidases and glutamic peptidases".Journal of Biochemistry.151(1): 13–25.doi:10.1093/jb/mvr129.PMID22016395.
  40. ^Hayes WK. 2005.Research on Biological Roles and Variation of Snake Venoms.Loma Linda University.

Further reading[edit]

External links[edit]

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