Structural basis of substrate specificity in the serine proteases

Protein Science

Volumn 4, Issue 3, 1995, Pages 337-360

  Perona, John J ^a,b   Craik, Charles S ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

enzyme kinetics; macromolecular recognition; protein engineering; protein structure; protein ligand interactions; serine protease; site directed mutagenesis; substrate specificity

Indexed keywords

SERINE PROTEINASE;

BINDING AFFINITY; ENZYME MODIFICATION; ENZYME SPECIFICITY; PRIORITY JOURNAL; PROTEIN STABILITY; REVIEW; STRUCTURE ACTIVITY RELATION;

AMINO ACID SEQUENCE; BINDING SITES; DNA MUTATIONAL ANALYSIS; MOLECULAR SEQUENCE DATA; PROTEIN ENGINEERING; SERINE ENDOPEPTIDASES; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY; SUPPORT, U.S. GOV'T, NON-P.H.S.; SUPPORT, U.S. GOV'T, P.H.S.;

EID: 0028914722     PISSN: 09618368     EISSN: 1469896X     Source Type: Journal    
DOI: 10.1002/pro.5560040301     Document Type: Review

References (186)

1. Engineering subtilisin and its substrates for efficient ligation of peptide bonds in aqueous solution
2. Nitrogen‐15 nuclear magnetic resonance spectroscopy. The state of histidine in the catalytic triad of α‐lytic protease. Implications for the charge‐relay mechanism of peptide‐bond cleavage by serine proteases
3. Free energy calculations by computer simulation
4. Active centers of Streptomyces griseus protease 1, Streptoinyces griseus protease 3, and α‐chymotrypsin: Enzyme‐substrate interactions
5. Active site of α‐lytic protease. Enzyme‐substrate interactions
6. The active centers of Streptomyces griseus protease 3 and α‐chymotrypsin: Enzyme‐substrate interactions remote from the scissile bond
7. Structural and catalytic models of trypsin‐like viral proteases
8. Mutational replacements in subtilisin 309. Val 104 has a modulating effect on the P4 substrate preference
9. Significance of hydrophobic S4‐P4 interactions in subtilisin 309 from Bacillus lentus
10. Chymotrypsins
11. Crystal structure of the alkaline proteinase savinase from Bacillus lentus at 1.4 Å resolution
12. Three‐dimensional structure of proteinase K at 0.15‐nm resolution
13. Structure of the complex of proteinase K with a substrate analogue hexapeptide inhibitor at 2.2‐Å resolution
14. Structure and mechanism of chymotrypsin
15. Role of a buried acid group in the mechanism of action of chymotrypsin
16. Refined 2 Å X‐ray crystal structure of porcine pancreatic kallikrein A, a specific trypsin‐like serine proteinase—Crystallization, structure determination, crystallographic refinement, structure and its comparison with bovine trypsin
17. The refined 1.9 Å crystal structure of human α‐thrombin: Interaction with D‐Phe‐Pro‐Arg chloromethyl ketone and significance of the Tyr‐Pro‐Pro‐Trp insertion segment
18. Human leukocyte and porcine pancreatic elastase: X‐ray crystal structures, mechanism, substrate specificity, and mechanism‐based inhibitors
19. Refined 1.2 Å crystal structure of the complex formed between subtilisin Carlsberg and the inhibitor eglin C. Molecular structure of eglin and its detailed interaction with subtilisin
20. The refined 2.2 Å X‐ray crystal structure of the ternary complex formed by bovine trypsinogen, valine‐valine and the Arg 15 analogue of bovine pancreatic trypsin inhibitor
21. X‐ray crystal structure of the complex of human leukocyte elastase (PMN elastase) and the third domain of the turkey ovomucoid inhibitor
22. Mutational remodeling of enzyme specificity
23. Structural analysis of specificity: α‐Lytic protease complexes with analogues of reaction intermediates
24. Structural basis for broad specificity in α‐lytic protease mutants
25. Serine protease mechanism: Structure of an inhibitory complex of α‐lytic protease and a tightly bound peptide boronic acid
26. Structural plasticity broadens the specificity of an engineered protease
27. The importance of a distal hydrogen bonding group in stabilizing the transition state in subtilisin BPN'
28. Molecular structure of the α‐lytic protease from Myxobacter 495 at 2.8 Å resolution
29. Structural and enzymatic characterization of a purified, prohormone‐processing enzyme: Secreted, soluble Kex2 protease
30. Site‐directed mutagenesis and the role of the oxyanion hole in subtilisin
31. Free energy calculations on binding and catalysis by α‐lytic protease: The role of substrate size in the P1 pocket
32. Conversion of the substrate specificity of mouse proteinase granzyme B
33. Probing the mechanism and improving the rate of substrate‐assisted catalysis in subtilisin BPN'
34. Engineering subtilisin BPN' for site‐specific proteolysis
35. Engineering enzyme specificity by “substrate‐assisted catalysis.”
36. Dissecting the catalytic triad of a serine protease
37. Functional interactions among catalytic residues in subtilisin BPN'
38. The role of Easter, an apparent serine protease, in organizing the dorsal‐ventral pattern of the Drosophila embryo
39. An investigation into the minimum requirements for peptide hydrolysis by mutation of the catalytic triad of trypsin
40. An alternate geometry for the catalytic triad of serine proteases
41. Trypsin display on the surface of bacteriophage
42. Redesigning trypsin: Alteration of substrate specificity
43. The catalytic role of the active site aspartic acid in serine proteases
44. Modulation of furin‐mediated proprotein processing activity by site‐directed mutagenesis
45. The epidermolytic toxins are serine proteases
46. The coagulation cascade: Initiation, maintenance and regulation
47. The 2.8 Å resolution structure of Streptomyces griseus protease B and its homology with α‐chymotrypsin and Streptomyces griseus protease A
48. 14C‐DIP‐trypsin with α‐chymotrypsin
49. The primary structure of staphylococcal protease
50. Hydrolysis of small peptide substrates parallels binding of chymotrypsin inhibitor 2 for mutants of subtilisin BPN'
51. A collagenolytic protease from the hepatopancreas of the fiddler crab, Uca pugilator. Purification and properties
52. Role of serine 214 and tyrosine 171, components of the S2 subsite of α‐lytic protease, in catalysis
53. Probing steric and hydrophobic effects on enzyme‐substrate interactions by protein engineering
54. Substrate specificity of trypsin investigated by using a genetic selection
55. Refined structure of α‐lytic protease at 1.7 Å resolution. Analysis of hydrogen bonding and solvent structure
56. Rat submaxillary gland serine protease, tonin — Structure solution and refinement at 1.8 Å resolution
57. 2+‐dependent serine protease
58. Selective alteration of substrate specificity by replacement of aspartic acid‐189 with lysine in the binding pocket of trypsin
59. Electrostatic complementarity in the substrate binding pocket of trypsin
60. Random mutagenesis of the substrate binding site of a serine protease can generate enzymes with increased activities and altered primary specificities
61. Substrate specificity of the collagenolytic serine protease from Uca pugilator: Studies with noncollagenous substrates
62. Amino acid sequence of a collagenolytic protease from the hepatopancreas of the fiddler crab, Uca pugilator
63. Comparative modeling methods: Application to the family of the mammalian serine proteases
64. Interdependency of the binding sites in subtilisin
65. Extensive comparison of the substrate preferences of two subtilisins as determined with peptide substrates which are based on the principle of intramolecular quenching
66. Molecular dynamics refinement of a thermitase‐eglin‐c complex at 1.98 Å resolution and comparison of two crystal forms that differ in calcium content
67. Kinetic and mechanistic characterization of a highly active hydrolytic antibody: Evidence for the formation of an acyl intermediate
68. Active site mapping of the serine proteases human leukocyte elastase, cathepsin G, porcine pancreatic elastase, rat mast cell proteases I and II, bovine chymotrypsin Aα and S. aureus protease V‐8 using tripeptide thiobenzyl ester substrates
69. Converting trypsin to chymotrypsin: Ground state binding does not determine substrate specificity
70. Converting trypsin to chymotrypsin: Residue 172 is a substrate specificity determinant
71. Converting trypsin to chymotrypsin: The role of surface loops
72. Introduction of a cysteine protease active site into trypsin
73. Regulation of serine protease activity by an engineered metal switch
74. Thrombin‐variable region 1. Evidence for the dominant contribution of VR1 of serine proteases to their interaction with plasminogen activator inhibitor 1
75. Structural basis of the activation and action of trypsin
76. Why ion pair reversal by protein engineering is unlikely to succeed
77. A designed peptide ligase for total synthesis of ribonuclease A with unnatural catalytic residues
78. Contribution of long‐range electrostatic interactions to the stabilization of the catalytic transition state of the serine protease subtilisin BPN'
79. Relationship between the structures and activities of some microbial serine proteases. II. Comparison of the tertiary structures of microbial and pancreatic serine proteases
80. Mutagenesis supports water mediated recognition in the trp repressor‐operator system
81. Dictionary of protein secondary structure: Pattern recognition of hydrogen‐bonded and geometrical features
82. Hydrolysis of a peptide bond in neutral water
83. Inhibition of the serine proteases leukocyte elastase, pancreatic elastase, cathepsin G and chymotrypsin by peptide boronic acids
84. Direct determination of the protonation states of aspartic acid‐102 and histidine‐57 in the tetrahedral intermediate of the serine proteases: Neutron structure of trypsin
85. Serine proteases: Structure and mechanism of catalysis
86. Cloning and functional expression of a cDNA encoding the catalytic subunit of bovine enterokinase
87. Proteases and post‐translational processing of prohormones: A review
88. Substrate specificity of the chymotrypsin‐like protease in secretory granules isolated from rat mast cells
89. Amino acid sequence of rat mast cell protease I (chymase)
90. Refined atomic model of wheat serine carboxypeptidase II at 2.2 Å resolution
91. Structure of wheat serine carboxypeptidase 11 at 3.5 Å resolution. A new class of serine protease
92. The preparation and properties of the catalytic subunit of bovine enterokinase
93. Novel serine proteases encoded by two cytotoxic T lymphocyte‐specific genes
94. Long‐range surface charge‐charge interactions in proteins. Comparison of experimental results with calculations from a theoretical method
95. Amino acid residues that affect interaction of tissue‐type plasminogen activator with plasminogen activator inhibitor 1
96. The apparent molecular weights of human intestinal aminopeptidase, enterokinase and maltase in native duodenal fluid
97. Subtilisins: Primary structure, chemical and physical properties
98. Catalytic groups of serine proteases. NMR investigations
99. Purification and specificity of porcine enterokinase
100. X‐ray structure of proteins
101. Three‐dimensional structure of tosyl‐α‐chymotrypsin
102. Substrate phage: Selection of protease substrates by monovalent phage display
103. Autocatalytic maturation of the prohormone convertase PC2
104. Structure of an engineered, metal‐actuated switch in trypsin
105. Perturbing the polar environment of Asp 102 in trypsin: Consequences of replacing conserved Ser 214
106. Crystal structures of two engineered thiol trypsins
107. Structural comparison of two serine proteinase‐protein inhibitor complexes: Eglin C‐subtilisin Carlsberg and CI‐2‐subtilisin Novo
108. Free energy perturbation calculations on binding and catalysis after mutating threonine 220 in subtilisin
109. Site‐directed mutagenesis on (serine) carboxypeptidase Y: A hydrogen‐bond network stabilizes the transition state by interaction with the C‐terminal carboxylate of the substrate
110. Electron density calculations as an extension of protein structure refinement. Streptomyces griseus protease A at 1.5 Å resolution
111. Comparative molecular model building of two serine proteinases from cytotoxic T lymphocytes
112. Peptide segment coupling catalyzed by the semisynthetic enzyme thiolsubtilisin
113. Structure of human factor D. A complement system protein at 2.0 Å resolution
114. Structure of human neutrophil elastase in complex with a peptide chloromethyl ketone inhibitor at 1.84 Å resolution
115. Evolution of proteolytic enzymes
116. Proteolytic enzymes, past and present
117. A glutamic acid specific serine protease utilizes a novel histidine triad in substrate binding
118. Cloning and sequence of a cDNA coding for the human beta‐migrating endothelialcell‐type plasminogen activator inhibitor
119. Human and murine cytotoxic T‐lymphocyte serine proteases: Subsite mapping with peptide thioester substrates and inhibition of enzyme activity and cytolysis by isocoumarins
120. The alpha/beta hydrolase fold
121. Crystal structure of trp repressor/operator at atomic resolution
122. Structure of human ds(1–45) factor Xa at 2.2 Å resolution
123. A genetic selection elucidates structural determinants of arginine versus lysine specificity in trypsin
124. Structural origins of substrate discrimination in trypsin and chymotrypsin
125. Exogenous acetate reconstitutes the enzymatic activity of Asp 189 Ser trypsin
126. Crystal structures of rat anionic trypsin complexed with the protein inhibitors APPI and BPTI
127. Relocating a negative charge in the binding pocket of trypsin
128. Structure and function of serine proteases
129. PH‐dependent mechanism in the catalysis of prolyl endopeptidase from pig muscle
130. Polypeptide halo‐methyl ketones bind to serine proteases as analogs of the tetrahedral intermediate
131. Mammalian chymotrypsin‐like enzymes. Comparative reactivities of rat mast cell proteases, human and dog skin chymases, and human cathepsin G with peptide 4‐nitroanilide substrates and with peptide chloromethyl ketone and sulfonyl fluoride inhibitors
132. Free energy perturbation calculations on binding and catalysis after mutating Asn 155 in subtilisin
133. Refined crystal structure of Streptomyces griseus trypsin at 1.7 Å resolution
134. PACE4 is a member of the mammalian propeptidase family that has overlapping but not identical substrate specificity to PACE
135. The structure of rat mast cell protease at 1.9‐Å resolution
136. Engineering a novel specificity in subtilisin BPN'
137. Variants of subtilisin BPN' with altered specificity profiles
138. An X‐ray crystallographic study of the binding of peptide chloromethyl ketone inhibitors to subtilisin BPN'
139. Subtilisin: A stereochemical mechanism involving transition‐state stabilization
140. Protein folding: Predicting predicting
141. Structure of the complex formed by bovine trypsin and bovine pancreatic trypsin inhibitor
142. Electrostatic effects on modification of charged groups in the active site cleft of subtilisin by protein engineering
143. Molecular cloning of human cathepsin G: Structural similarity to mast cell and cytotoxic T lymphocyte proteinases
144. On the size of the active site in proteases. I. Papain
145. Mapping the S' subsites of serine proteases using acyl transfer to mixtures of peptide nucleophiles
146. Role of the S' subsites in serine protease catalysis. Active‐site mapping of rat chymotrypsin, rat trypsin, α‐lytic protease and cercarial protease from Schistosoma mansoni
147. Mammalian neural and endocrine pro‐protein and pro‐hormone convertases belonging to the subtilisin family of serine proteases
148. Molecular cloning of a cDNA that encodes a serine protease with chymotryptic and collagenolytic activities in the hepatopancreas of the shrimp Penaeus vanameii (Crustacea, Decapoda)
149. Determinants of repressor‐operator recognition from the structure of the trp operator binding site
150. α‐tosyl‐L‐lysine
151. Engineering of the substrate‐binding region of the subtilisin‐like, cell‐envelope proteinase of Lactococcus lactis
152. Homology modelling and protein engineering strategy of subtilases, the family of subtilisin‐like serine proteases
153. Primary structure of human neutrophil elastase
154. Identification of a cDNA encoding a second putative prohormone convertase related to PC2 in AtT20 cells and islets of Langerhans
155. Ventralizing signal determined by protease activation in Drosophila embryogenesis
156. Mutational replacements of the amino acid residues forming the hydrophobic S4 binding pocket of subtilisin 309 from Bacillus lentus
157. The three‐dimensional structure of Asn 102 mutant of trypsin: Role of Asp 102 in serine protease catalysis
158. Catalysis by human leukocyte elastase: Mechanistic insights into specificity requirements
159. Crystallographic and NMR studies of the serine proteases
160. A family of protein‐cutting proteins
161. The primary structure of the glutamic acid‐specific protease of Streftomyces griseus
162. Molecular recognition at the active site of subtilisin BPN': Crystallographic studies using genetically engineered proteinaceous inhibitor SSI (Streptomyces subtilisin inhibitor)
163. Refined crystal structure of the complex of subtilisin BPN' and Streptomyces subtilisin inhibitor at 1.8 Å resolution
164. Protein engineering of the high‐alkaline serine protease PB92 from Bacillus alcalophilus: Functional and structural consequences of mutation at the S4 substrate binding pocket
165. Dependence of the kinetic parameters for elastase‐catalyzed amide hydrolysis on the length of peptide substrates
166. The substrate specificity of Uca pugilator collagenolytic serine protease 1 correlates with the bovine type I collagen cleavage sites
167. Structural homology between the human fur gene product and the subtilisin‐like protease encoded by yeast KEX2
168. Crystal structure of the high‐alkaline serine protease PB92 from Bacillus alcalophilus
169. Structure and function of eukaryotic proprotein processing enzymes of the subtilisin family of serine proteases
170. How do serine proteases really work?
171. Three‐dimensional Fourier synthesis of tosyl elastase at 3.5 Å resolution
172. The refined 2.3 Å crystal structure of human leukocyte elastase in a complex with a valine chloromethyl ketone inhibitor
173. Importance of hydrogen bond formation in stabilizing the transition state of subtilisin
174. Recruitment of substrate‐specificity properties from one enzyme into a related one by protein engineering
175. On the evolution of specificity and catalysis in subtilisin
176. Subtilisin—An enzyme designed to be engineered
177. Designing substrate specificity by protein engineering of electrostatic interactions
178. Crystallographic analysis of trypsin G226A. A specificity pocket mutant of rat trypsin with altered binding and catalysis
179. Computational method for the design of enzymes with altered substrate specificity
180. A major serine protease in rat skeletal muscle: Evidence for its mast cell origin
181. Immunofluorescent localization of a serine protease in rat small intestine
182. Structure of subtilisin BPN' at 2.5 Å resolution
183. Substrate specificity of two chymotrypsin‐like proteases from rat mast cells. Studies with peptide 4‐nitroanilides and comparison with cathepsin G
184. The kinetic consequences of the acyl‐enzyme mechanism for the reactions of specific substrates with chymotrypsin
185. The three‐dimensional structure of a catalytic antibody with active site similarity to serine proteases