1. Enzimologija Nastavnik: Tanja Ćirković Veličković

2. Pregled Opšte informacie o predmetu i načinu ocenjivanja Opšte informacie o predmetu i načinu ocenjivanja Literatura Literatura Opšti pojmovi Opšti pojmovi Nomenklatura enzima Nomenklatura enzima Uvodna znanja Uvodna znanja

3. Program i organizacija vežbi Teorijske vezbe – izračunavanja u enzimologiji Teorijske vezbe – izračunavanja u enzimologiji Laboratorijske vežbe: osnovna odredjivanja u enzimologiji Laboratorijske vežbe: osnovna odredjivanja u enzimologiji Laboratorijske vežbe: Razni aspekti primene enzima Laboratorijske vežbe: Razni aspekti primene enzima Fond časova predavanja i vežbi: 3 + 3 (teorijske vežbe) Asistent: Marija Stojadinovic i Dragana Stanic

4. Način ocenjivanja Predavanja: 10 bodova Predavanja: 10 bodova Kolokvijum 1: 20 bodova Kolokvijum 1: 20 bodova Kolokvijum 2: 20 bodova Kolokvijum 2: 20 bodova Seminarski rad: 5 bodova Seminarski rad: 5 bodova Problemski zadatak: 20 bodova Problemski zadatak: 20 bodova Usmeni deo ispita: 25 bodova Usmeni deo ispita: 25 bodova

5. Literatura Structure and mechanism in protein science, Alan Fersht Structure and mechanism in protein science, Alan Fersht Enzimologija: Laboratorijski priručnik, Radivoje Prodanović i Tanja Ćirković Veličković Enzimologija: Laboratorijski priručnik, Radivoje Prodanović i Tanja Ćirković Veličković Zbirka zadataka iz enzimologije, Ivanka Karadžić Zbirka zadataka iz enzimologije, Ivanka Karadžić

6. Enzyme catalysis, not different, just better! Katalizator je supstanca koja dovodi do ubrzanja hemijske reakcije, tako da se pri tom promena G ne menja (IUPAC, 1981.) Katalizator je supstanca koja dovodi do ubrzanja hemijske reakcije, tako da se pri tom promena G ne menja (IUPAC, 1981.) Biološki katalizatori: Biološki katalizatori: Proteini (enzimi, abzimi) RNK (ribozimi) Mimetici enzima - Šta enzim radi? Struktura proteina – enzima Hemijska kinetika – enzimska kinetika

7. Sukcinat dehidrogenaza sa vezanim hemom (prostetičnom grupom) Enzim Enzim MonomeranMonomeran Homo/hetero dimeran, trimeran etcHomo/hetero dimeran, trimeran etc OligomeranOligomeran Multienzimski kompleksiMultienzimski kompleksi Holoenzim (apoenzim + kofaktor/koenzim)Holoenzim (apoenzim + kofaktor/koenzim) KofaktorKofaktor KoenzimKoenzim Prosteticna grupa (čvrsto vezan kofaktor)Prosteticna grupa (čvrsto vezan kofaktor)

8. Nomenklatura Trivijalna imena enzima Trivijalna imena enzima E.C. nomenklatura E.C. nomenklatura

9. E.C. Nomenklatura enzima Recommendations of the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology on the Nomenclature and Classification of Enzymes by the Reactions they Catalyse Recommendations of the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology on the Nomenclature and Classification of Enzymes by the Reactions they Catalyse http://www.chem.qmul.ac.uk/iubmb/en zyme/ http://www.chem.qmul.ac.uk/iubmb/en zyme/

10. EC 1.1 Oksidoreduktaze EC 1.1 Oksidoreduktaze Acting on the CH-OH group of donors Acting on the CH-OH group of donors Contents EC 1.1.1 With NAD or NADP as acceptor Contents EC 1.1.1 With NAD or NADP as acceptorEC 1.1.1EC 1.1.1 EC 1.1.2 With a cytochrome as acceptor EC 1.1.2 With a cytochrome as acceptor EC 1.1.2 EC 1.1.2 EC 1.1.3 With oxygen as acceptor EC 1.1.3 With oxygen as acceptor EC 1.1.3 EC 1.1.3 EC 1.1.4 With a disulfide as acceptor EC 1.1.4 With a disulfide as acceptor EC 1.1.4 EC 1.1.4 EC 1.1.5 With a quinone or similar compound as acceptor EC 1.1.5 With a quinone or similar compound as acceptor EC 1.1.5 EC 1.1.5 EC 1.1.99 With other acceptors EC 1.1.99 With other acceptors EC 1.1.99 EC 1.1.99 EC 2EC 2 Transferaze EC 2 EC 3EC 3 Hidrolaze EC 3 EC 4EC 4 Liaze EC 4 EC 5EC 5 Izomeraze EC 5 EC 6EC 6 Ligaze EC 6

11. EC 1 Oxidoreductases EC 1 Oxidoreductases EC 1 EC 1 EC 1.1Acting on the CH-OH group of donors EC 1.1Acting on the CH-OH group of donors EC 1.2Acting on the aldehyde or oxo group of donors EC 1.2Acting on the aldehyde or oxo group of donors EC 1.3Acting on the CH-CH group of donors EC 1.3Acting on the CH-CH group of donors EC 1.4Acting on the CH-NH 2 group of donors EC 1.4Acting on the CH-NH 2 group of donors EC 1.5Acting on the CH-NH group of donors EC 1.5Acting on the CH-NH group of donors EC 1.6Acting on NADH or NADPH EC 1.6Acting on NADH or NADPH EC 1.7Acting on other nitrogenous compounds as donors EC 1.7Acting on other nitrogenous compounds as donors EC 1.8Acting on a sulfur group of donors EC 1.8Acting on a sulfur group of donors EC 1.9Acting on a heme group of donors EC 1.9Acting on a heme group of donors EC 1.10Acting on diphenols and related substances as donors EC 1.10Acting on diphenols and related substances as donors EC 1.11Acting on a peroxide as acceptor EC 1.11Acting on a peroxide as acceptor EC 1.12Acting on hydrogen as donor EC 1.12Acting on hydrogen as donor EC 1.13Acting on single donors with incorporation of molecular oxygen (oxygenases) EC 1.13Acting on single donors with incorporation of molecular oxygen (oxygenases) EC 1.14Acting on paired donors, with incorporation or reduction of molecular oxygen EC 1.14Acting on paired donors, with incorporation or reduction of molecular oxygen EC 1.15Acting on superoxide radicals as acceptor EC 1.15Acting on superoxide radicals as acceptor EC 1.16Oxidising metal ions EC 1.16Oxidising metal ions EC 1.17Acting on CH or CH 2 groups EC 1.17Acting on CH or CH 2 groups EC 1.18Acting on iron-sulfur proteins as donors EC 1.18Acting on iron-sulfur proteins as donors EC 1.19Acting on reduced flavodoxin as donor EC 1.19Acting on reduced flavodoxin as donor EC 1.20Acting on phosphorus or arsenic in donors EC 1.20Acting on phosphorus or arsenic in donors EC 1.21Acting on X-H and Y-H to form an X-Y bond EC 1.21Acting on X-H and Y-H to form an X-Y bond EC 1.97Other oxidoreductases EC 1.97Other oxidoreductases

12. E.C. vs. Trivijalna nomenklatura EC 1.1.1.1 alcohol dehydrogenase EC 1.1.1.2 alcohol dehydrogenase (NADP+) EC 1.1.1.3 homoserine dehydrogenase EC 1.1.1.4 (R,R)-butanediol dehydrogenase EC 1.1.1.5 acetoin dehydrogenase EC 1.1.1.6 glycerol dehydrogenase EC 1.1.1.7 propanediol-phosphate dehydrogenase EC 1.1.1.8 glycerol-3-phosphate dehydrogenase (NAD+) EC 1.1.1.9 D-xylulose reductase EC 1.1.1.10 L-xylulose reductase EC 1.1.1.1 alcohol dehydrogenase EC 1.1.1.2 alcohol dehydrogenase (NADP+) EC 1.1.1.3 homoserine dehydrogenase EC 1.1.1.4 (R,R)-butanediol dehydrogenase EC 1.1.1.5 acetoin dehydrogenase EC 1.1.1.6 glycerol dehydrogenase EC 1.1.1.7 propanediol-phosphate dehydrogenase EC 1.1.1.8 glycerol-3-phosphate dehydrogenase (NAD+) EC 1.1.1.9 D-xylulose reductase EC 1.1.1.10 L-xylulose reductase EC 1.1.1.1 EC 1.1.1.2 EC 1.1.1.3 EC 1.1.1.4 EC 1.1.1.5 EC 1.1.1.6 EC 1.1.1.7 EC 1.1.1.8 EC 1.1.1.9 EC 1.1.1.10 EC 1.1.1.1 EC 1.1.1.2 EC 1.1.1.3 EC 1.1.1.4 EC 1.1.1.5 EC 1.1.1.6 EC 1.1.1.7 EC 1.1.1.8 EC 1.1.1.9 EC 1.1.1.10

13. http://www.chem.qmul.ac.uk/iubmb/ enzyme/search.html http://www.chem.qmul.ac.uk/iubmb/ enzyme/search.html http://www.chem.qmul.ac.uk/iubmb/ enzyme/search.html http://www.chem.qmul.ac.uk/iubmb/ enzyme/search.html

14. Searching the Enzyme list Searching the Enzyme list This search form looks at IUBMB Enzyme Nomenclature with a URL starting http://www.chem.qmul.ac.uk/iubmb/enzyme/ All recommended Enzymes are listed on the web. This search excludes other biochemical recommendations on enzyme kinetics, biochemical thermodynamics, and recommendations made by IUBMB only. To search these click here or for more chemical recommendations and other IUPAC recommendations click here. This search form looks at IUBMB Enzyme Nomenclature with a URL starting http://www.chem.qmul.ac.uk/iubmb/enzyme/ All recommended Enzymes are listed on the web. This search excludes other biochemical recommendations on enzyme kinetics, biochemical thermodynamics, and recommendations made by IUBMB only. To search these click here or for more chemical recommendations and other IUPAC recommendations click here.click hereclick here.click hereclick here. Search: PEPSIN Search: PEPSIN Some search terms cause problems: For (S)-stylopine use stylopine otherwise all references with S as an initial are included. For germacrene A use "germacrene A" Some search terms cause problems: For (S)-stylopine use stylopine otherwise all references with S as an initial are included. For germacrene A use "germacrene A"

15. Web Results 1 - 10 of about 32 for pepsin [definition]. (0.06 seconds) Web Results 1 - 10 of about 32 for pepsin [definition]. (0.06 seconds) definition EC 3.4.23 EC 3.4.23 EC 3.4.23 EC 3.4.23 EC 3.4.23. Aspartic endopeptidases. Contents. EC 3.4.23.1 pepsin A EC 3.4.23.2 pepsin B EC 3.4.23.3 gastricsin EC 3.4.23.4 chymosin EC 3.4.23.5 cathepsin D... www.chem.qmul.ac.uk/iubmb/enzyme/EC3/4/23/ - 5k - Cached - Similar pages EC 3.4.23. Aspartic endopeptidases. Contents. EC 3.4.23.1 pepsin A EC 3.4.23.2 pepsin B EC 3.4.23.3 gastricsin EC 3.4.23.4 chymosin EC 3.4.23.5 cathepsin D... www.chem.qmul.ac.uk/iubmb/enzyme/EC3/4/23/ - 5k - Cached - Similar pagesCachedSimilar pagesCachedSimilar pages EC 3.4.23.1 EC 3.4.23.1 EC 3.4.23.1 EC 3.4.23.1 Human pepsin A occurs in five molecular forms. Pig pepsin D [1,2] is... Lee, D. and Ryle, A.P. Pepsin D. A minor component of commercial pepsin... www.chem.qmul.ac.uk/iubmb/enzyme/EC3/4/23/1.html - 5k - Cached - Similar pages Human pepsin A occurs in five molecular forms. Pig pepsin D [1,2] is... Lee, D. and Ryle, A.P. Pepsin D. A minor component of commercial pepsin... www.chem.qmul.ac.uk/iubmb/enzyme/EC3/4/23/1.html - 5k - Cached - Similar pages CachedSimilar pages CachedSimilar pages EC 3.4.23.18 EC 3.4.23.18 EC 3.4.23.18 EC 3.4.23.18 In peptidase family A1 (pepsin A family). Formerly included in EC 3.4.23.6... proteinase of Aspergillus awamori - an analog of penicillopepsin and pepsin.... www.chem.qmul.ac.uk/iubmb/enzyme/EC3/4/23/18.html - 7k - Cached - Similar pages In peptidase family A1 (pepsin A family). Formerly included in EC 3.4.23.6... proteinase of Aspergillus awamori - an analog of penicillopepsin and pepsin.... www.chem.qmul.ac.uk/iubmb/enzyme/EC3/4/23/18.html - 7k - Cached - Similar pages CachedSimilar pages CachedSimilar pages EC 3.4.23.3 EC 3.4.23.3 EC 3.4.23.3 EC 3.4.23.3 Other names: pepsin C; pig parapepsin II; parapepsin II... In peptidase family A1 (pepsin A family). Formerly EC 3.4.4.22. Links to other databases: BRENDA... www.chem.qmul.ac.uk/iubmb/enzyme/EC3/4/23/3.html - 4k - Cached - Similar pages Other names: pepsin C; pig parapepsin II; parapepsin II... In peptidase family A1 (pepsin A family). Formerly EC 3.4.4.22. Links to other databases: BRENDA... www.chem.qmul.ac.uk/iubmb/enzyme/EC3/4/23/3.html - 4k - Cached - Similar pages CachedSimilar pages CachedSimilar pages

16. IUBMB Enzyme Nomenclature IUBMB Enzyme Nomenclature EC 3.4.23.1 EC 3.4.23.1 Accepted name: pepsin A Accepted name: pepsin A Reaction: Preferential cleavage: hydrophobic, preferably aromatic, residues in P1 and P1' positions. Cleaves Phe1 Val, Gln4 His, Glu13 Ala, Ala14 Leu, Leu15 Tyr, Tyr16 Leu, Gly23 Phe, Phe24 Phe and Phe25 Tyr bonds in the B chain of insulin Reaction: Preferential cleavage: hydrophobic, preferably aromatic, residues in P1 and P1' positions. Cleaves Phe1 Val, Gln4 His, Glu13 Ala, Ala14 Leu, Leu15 Tyr, Tyr16 Leu, Gly23 Phe, Phe24 Phe and Phe25 Tyr bonds in the B chain of insulin Other names: pepsin; lactated pepsin; pepsin fortior; fundus-pepsin; elixir lactate of pepsin; P I; lactated pepsin elixir; P II; pepsin R; pepsin D Other names: pepsin; lactated pepsin; pepsin fortior; fundus-pepsin; elixir lactate of pepsin; P I; lactated pepsin elixir; P II; pepsin R; pepsin D Comments: The predominant endopeptidase in the gastric juice of vertebrates, formed from pepsinogen A by limited proteolysis. Human pepsin A occurs in five molecular forms. Pig pepsin D [1,2] is unphosphorylated pepsin A. Type example of peptidase family A1. Formerly EC 3.4.4.1 Comments: The predominant endopeptidase in the gastric juice of vertebrates, formed from pepsinogen A by limited proteolysis. Human pepsin A occurs in five molecular forms. Pig pepsin D [1,2] is unphosphorylated pepsin A. Type example of peptidase family A1. Formerly EC 3.4.4.1peptidase family A1peptidase family A1 Links to other databases: BRENDA, EXPASY, GTD, MEROPS, PDB, CAS registry number: 9001-75-6 Links to other databases: BRENDA, EXPASY, GTD, MEROPS, PDB, CAS registry number: 9001-75-6BRENDAEXPASYGTDMEROPSPDBBRENDAEXPASYGTDMEROPSPDB References: References: 1. Lee, D. and Ryle, A.P. Pepsinogen D. A fourth proteolytic zymogen from pig gastric mucosa. Biochem. J. 104 (1967) 735-741. [PMID: 4167464] 1. Lee, D. and Ryle, A.P. Pepsinogen D. A fourth proteolytic zymogen from pig gastric mucosa. Biochem. J. 104 (1967) 735-741. [PMID: 4167464]4167464 2. Lee, D. and Ryle, A.P. Pepsin D. A minor component of commercial pepsin preparations. Biochem. J. 104 (1967) 742-748. [PMID: 4860638] 2. Lee, D. and Ryle, A.P. Pepsin D. A minor component of commercial pepsin preparations. Biochem. J. 104 (1967) 742-748. [PMID: 4860638] 4860638 3. Foltmann, R. Gastric proteinases -structure, function, evolution and mechanism of action. Essays Biochem. 17 (1981) 52-84. [PMID: 6795036] 3. Foltmann, R. Gastric proteinases -structure, function, evolution and mechanism of action. Essays Biochem. 17 (1981) 52-84. [PMID: 6795036]6795036 4. James, M.N.G. and Sielecki, A.R. Molecular structure of an aspartic proteinase zymogen, porcine pepsinogen, at 1.8 Å resolution. Nature 319 (1986) 33-38. [PMID: 3941737] 4. James, M.N.G. and Sielecki, A.R. Molecular structure of an aspartic proteinase zymogen, porcine pepsinogen, at 1.8 Å resolution. Nature 319 (1986) 33-38. [PMID: 3941737]3941737 5. Fruton, J.S. Aspartyl proteinases. In New Comprehensive Biochemistry Vol. 16, Hydrolytic Enzymes (Neuberger, A. and Brocklehurst, K., eds), pp. 1-38 (1987) Elsevier, Amsterdam 5. Fruton, J.S. Aspartyl proteinases. In New Comprehensive Biochemistry Vol. 16, Hydrolytic Enzymes (Neuberger, A. and Brocklehurst, K., eds), pp. 1-38 (1987) Elsevier, Amsterdam 6. Tang, J. and Wong, R.N.S. Evolution in the structure and function of aspartic proteases. J. Cell. Biochem. 33 (1987) 53-63. [PMID: 3546346] 6. Tang, J. and Wong, R.N.S. Evolution in the structure and function of aspartic proteases. J. Cell. Biochem. 33 (1987) 53-63. [PMID: 3546346]3546346 7. Pohl, J. and Dunn, B.M. Secondary enzyme-substrate interactions: kinetic evidence for ionic interactions between substrate side chains and the pepsin active site. Biochemistry 27 (1988) 4827-4834. [PMID: 3139029] 7. Pohl, J. and Dunn, B.M. Secondary enzyme-substrate interactions: kinetic evidence for ionic interactions between substrate side chains and the pepsin active site. Biochemistry 27 (1988) 4827-4834. [PMID: 3139029]3139029

17. acetyl-L-phenylalanyl-L-diiodotyrosine +H2O =acetyl-L-phenylalanine +L-diiodotyrosine

18. PDB: x-ray struktura pepsina u kompleksu sa inhibitorom