Amino acid replacements can selectively affect the interaction energy of autonomous folding units in the alpha subunit of tryptophan synthase.


Abstract

Amino acid replacements were made at the interface between two autonomous folding units in the alpha subunit of tryptophan synthase from Salmonella typhimurium to test their mutual interaction energy. The results of equilibrium studies of the urea-induced unfolding reaction of the wild-type and mutant proteins in which phenylalanine 22 is replaced by leucine, isoleucine, and valine can be understood in terms of a selective decrease in the interaction energy between the two folding units; the intrinsic stability of each folding unit is not significantly altered. Kinetic studies of the rate-limiting step in unfolding show that the interaction energy appears in the transition state preceding the native conformation. Comparisons of the individual effects of these nonpolar side chains show that both hydrophobic and steric effects play important roles in the interaction energy between the folding units. The implication of these results is that the high cooperativity observed in the folding of many globular proteins may be reduced by appropriate amino acid replacements. Study holds ProTherm entries: 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247 Extra Details: additive : K2EDTA(5 mM), alpha subunit of tryptophan synthase; interaction energy;,hydrophobic; amino acid replacements

Submission Details

ID: DuJphBqK3

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:14 p.m.

Version: 1

Publication Details
Chen X;Rambo R;Matthews CR,Biochemistry (1992) Amino acid replacements can selectively affect the interaction energy of autonomous folding units in the alpha subunit of tryptophan synthase. PMID:1540577
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
5CGQ 2016-07-13 1.18 Crystal structure of Tryptophan Synthase from Salmonella typhimurium in complex with F9 ligand in the alpha-site and the product L-Tryptophan in the beta-site.
4HT3 2014-01-01 1.3 The crystal structure of Salmonella typhimurium Tryptophan Synthase at 1.30A complexed with N-(4'-TRIFLUOROMETHOXYBENZENESULFONYL)-2-AMINO-1-ETHYLPHOSPHATE (F9) inhibitor in the alpha site, internal aldimine
1QOP 2000-11-10 1.4 CRYSTAL STRUCTURE OF WILD-TYPE TRYPTOPHAN SYNTHASE COMPLEXED WITH INDOLE PROPANOL PHOSPHATE
6DZ4 2019-07-10 1.45 Crystal structure of Salmonella typhimurium Tryptophan Synthase with sodium ion at the metal coordination site and [3-hydroxy-2-methyl-5-phosphonooxymethyl-pyridin-4-ylmethyl]-serine (PLS) at the beta-site.
4HPJ 2013-12-25 1.45 Crystal structure of Tryptophan Synthase at 1.45 A resolution in complex with 2-aminophenol quinonoid in the beta site and the F9 inhibitor in the alpha site
1K8Y 2002-06-19 1.5 CRYSTAL STRUCTURE OF THE TRYPTOPHAN SYNTHASE BETA-SER178PRO MUTANT COMPLEXED WITH D,L-ALPHA-GLYCEROL-3-PHOSPHATE
2CLK 2007-06-12 1.5 Tryptophan Synthase in complex with D-glyceraldehyde 3-phosphate (G3P)
1TJP 2005-12-27 1.5 Crystal Structure Of Wild-Type Tryptophan Synthase Complexed With 1-[(2-hydroxylphenyl)amino]3-glycerolphosphate
2CLO 2007-06-12 1.5 Tryptophan Synthase (external aldimine state) in complex with (naphthalene-2'-sulfonyl)-2-amino-1-ethylphosphate (F19)
2CLE 2007-06-12 1.5 Tryptophan Synthase in complex with N-(4'-trifluoromethoxybenzoyl)-2- amino-1-ethylphosphate (F6) - lowF6 complex
1WBJ 2006-05-24 1.5 wildtype tryptophan synthase complexed with glycerol phosphate
1KFC 2003-01-07 1.5 CRYSTAL STRUCTURE OF ALPHAT183V MUTANT OF TRYPTOPHAN SYNTHASE FROM SALMONELLA TYPHIMURIUM With Indole Propanol Phosphate
2CLM 2007-06-12 1.51 Tryptophan Synthase (external aldimine state) in complex with N-(4'- trifluoromethoxybenzoyl)-2-amino-1-ethylphosphate (F6F)
4ZQC 2016-02-10 1.54 Tryptophan Synthase from Salmonella typhimurium in complex with two molecules of N-(4'-trifluoromethoxybenzoyl)-2-amino-1-ethylphosphate (F6F) inhibitor in the alpha-site and a single F6F molecule in the beta-site at 1.54 Angstrom resolution.
2CLL 2007-06-12 1.6 Tryptophan Synthase (external aldimine state) in complex with N-(4'- trifluoromethoxybenzenesulfonyl)-2-amino-1-ethylphosphate (F9)
4HN4 2013-12-25 1.64 Tryptophan synthase in complex with alpha aminoacrylate E(A-A) form and the F9 inhibitor in the alpha site
6D0V 2019-04-17 1.64 Tryptophan synthase Q114A mutant in complex with inhibitor N-(4'-trifluoromethoxybenzenesulfonyl)-2-amino-1-ethylphosphate (F9F) at the alpha-site, aminoacrylate (P1T) at the beta site, and cesium ion at the metal coordination site
6DZO 2019-07-10 1.64 Crystal structure of Salmonella typhimurium Tryptophan Synthase mutant beta-Q114A with 2-({[4-(trifluoromethoxy)phenyl]sulfonyl}amino)ethyl dihydrogen phosphate (F9F) at the alpha-site, Cesium ion at the metal coordination site, and [3-hydroxy-2-methyl-5-phosphonooxymethyl-pyridin-4-ylmethyl]-serine (PLS) at the beta-site.
4HPX 2013-12-18 1.65 Crystal structure of Tryptophan Synthase at 1.65 A resolution in complex with alpha aminoacrylate E(A-A) and benzimidazole in the beta site and the F9 inhibitor in the alpha site
4Y6G 2016-02-10 1.65 Crystal structure of Tryptophan Synthase from Salmonella typhimurium in complex with N-(4'-trifluoromethoxybenzoyl)-2-amino-1-ethylphosphate (F6F) inhibitor in the alpha-site and beta-site.
6C73 2019-01-23 1.65 Tryptophan synthase Q114A mutant (internal aldimine state) in complex with N-(4'-trifluoromethoxybenzenesulfonyl)-2-amino-1-ethylphosphate (F9F) with cesium ion bound in the metal coordination site
4XUG 2016-01-27 1.65 Crystal structure of Tryptophan Synthase from Salmonella typhimurium in complex with 2-({[4-(Trifluoromethoxy)Phenyl]Sulfonyl}Amino)Ethyl Dihydrogen Phosphate (F9F) inhibitor in the alpha site and ammonium ion in the metal coordination site.
2CLI 2007-06-12 1.7 Tryptophan Synthase in complex with N-(4'- trifluoromethoxybenzenesulfonyl)-2-amino-1-ethylphosphate (F9)
2CLH 2007-06-12 1.7 Tryptophan Synthase in complex with (naphthalene-2'-sulfonyl)-2-amino- 1-ethylphosphate (F19)
2RH9 2007-11-06 1.7 Tryptophan synthase complexed with IGP, internal aldimine, pH 9.0
1K7X 2002-06-19 1.7 CRYSTAL STRUCTURE OF THE BETA-SER178PRO MUTANT OF TRYPTOPHAN SYNTHASE
1K8Z 2002-06-19 1.7 CRYSTAL STRUCTURE OF THE TRYPTOPHAN SYNTHASE BETA-SER178PRO MUTANT COMPLEXED WITH N-[1H-INDOL-3-YL-ACETYL]GLYCINE ACID
2CLF 2007-06-26 1.7 Tryptophan Synthase in complex with N-(4'-trifluoromethoxybenzoyl)-2- amino-1-ethylphosphate (F6) - highF6 complex
1K3U 2002-07-03 1.7 CRYSTAL STRUCTURE OF WILD-TYPE TRYPTOPHAN SYNTHASE COMPLEXED WITH N-[1H-INDOL-3-YL-ACETYL]ASPARTIC ACID
1KFE 2003-01-07 1.75 CRYSTAL STRUCTURE OF ALPHAT183V MUTANT OF TRYPTOPHAN SYNTHASE FROM SALMONELLA TYPHIMURIUM WITH L-Ser Bound To The Beta Site
4WX2 2015-11-18 1.75 Crystal structure of Tryptophan Synthase from Salmonella typhimurium in complex with two F6F molecules in the alpha-site and one F6F molecule in the beta-site
4KKX 2014-01-01 1.77 Crystal structure of Tryptophan Synthase from Salmonella typhimurium with 2-aminophenol quinonoid in the beta site and the F6 inhibitor in the alpha site
2J9Z 2007-12-04 1.8 Tryptophan Synthase T110 mutant complex
1KFJ 2003-10-21 1.8 CRYSTAL STRUCTURE OF WILD-TYPE TRYPTOPHAN SYNTHASE COMPLEXED WITH L-SERINE
2J9Y 2007-12-04 1.8 Tryptophan Synthase Q114N mutant in complex with Compound II
1QOQ 2000-11-10 1.8 CRYSTAL STRUCTURE OF WILD-TYPE TRYPTOPHAN SYNTHASE COMPLEXED WITH INDOLE GLYCEROL PHOSPHATE
5BW6 2016-02-10 1.82 Tryptophan Synthase from Salmonella typhimurium in complex with a single molecule of 2-({[4-(trifluoromethoxy)phenyl]carbonyl}amino)ethyl dihydrogen phosphate (F6) in the alpha-site.
3PR2 2011-02-09 1.85 Tryptophan synthase indoline quinonoid structure with F9 inhibitor in alpha site
1A5A 1998-05-27 1.9 CRYO-CRYSTALLOGRAPHY OF A TRUE SUBSTRATE, INDOLE-3-GLYCEROL PHOSPHATE, BOUND TO A MUTANT (ALPHAD60N) TRYPTOPHAN SYNTHASE ALPHA2BETA2 COMPLEX REVEALS THE CORRECT ORIENTATION OF ACTIVE SITE ALPHA GLU 49
1BEU 1998-08-12 1.9 TRP SYNTHASE (D60N-IPP-SER) WITH K+
1UBS 1996-03-08 1.9 TRYPTOPHAN SYNTHASE (E.C.4.2.1.20) WITH A MUTATION OF LYS 87->THR IN THE B SUBUNIT AND IN THE PRESENCE OF LIGAND L-SERINE
2J9X 2007-06-26 1.9 Tryptophan Synthase in complex with GP, alpha-D,L-glycerol-phosphate, Cs, pH6.5 - alpha aminoacrylate form - (GP)E(A-A)
1K8X 2002-12-18 1.9 Crystal Structure Of AlphaT183V Mutant Of Tryptophan Synthase From Salmonella Typhimurium
1K7F 2002-07-10 1.9 CRYSTAL STRUCTURE OF WILD-TYPE TRYPTOPHAN SYNTHASE COMPLEXED WITH N-[1H-INDOL-3-YL-ACETYL]VALINE ACID
1KFB 2003-01-07 1.9 CRYSTAL STRUCTURE OF ALPHAT183V MUTANT OF TRYPTOPHAN SYNTHASE FROM SALMONELLA TYPHIMURIUM WITH Indole Glycerol Phosphate
2TYS 1997-04-01 1.9 CRYSTAL STRUCTURES OF MUTANT (BETAK87T) TRYPTOPHAN SYNTHASE ALPHA2 BETA2 COMPLEX WITH LIGANDS BOUND TO THE ACTIVE SITES OF THE ALPHA AND BETA SUBUNITS REVEAL LIGAND-INDUCED CONFORMATIONAL CHANGES
1TTQ 1996-03-08 2.0 TRYPTOPHAN SYNTHASE (E.C.4.2.1.20) IN THE PRESENCE OF POTASSIUM AT ROOM TEMPERATURE
2RHG 2007-11-20 2.0 Tryptophan synthase complexed with IGP, pH 7.0, internal aldimine
1A5B 1998-05-27 2.0 CRYO-CRYSTALLOGRAPHY OF A TRUE SUBSTRATE, INDOLE-3-GLYCEROL PHOSPHATE, BOUND TO A MUTANT (ALPHA D60N) TRYPTOPHAN SYNTHASE ALPHA2BETA2 COMPLEX REVEALS THE CORRECT ORIENTATION OF ACTIVE SITE ALPHA GLU 49
1CW2 1999-12-21 2.0 CRYSTAL STRUCTURE OF THE COMPLEX OF BACTERIAL TRYPTOPHAN SYNTHASE WITH THE TRANSITION STATE ANALOGUE INHIBITOR 4-(2-HYDROXYPHENYLSULFINYL)-BUTYLPHOSPHONIC ACID
2TRS 1997-04-01 2.04 CRYSTAL STRUCTURES OF MUTANT (BETAK87T) TRYPTOPHAN SYNTHASE ALPHA2 BETA2 COMPLEX WITH LIGANDS BOUND TO THE ACTIVE SITES OF THE ALPHA AND BETA SUBUNITS REVEAL LIGAND-INDUCED CONFORMATIONAL CHANGES
3CEP 2008-04-01 2.1 Structure of a tryptophan synthase quinonoid intermediate
1BKS 1999-03-23 2.2 TRYPTOPHAN SYNTHASE (E.C.4.2.1.20) FROM SALMONELLA TYPHIMURIUM
1C8V 2000-01-13 2.2 CRYSTAL STRUCTURE OF THE COMPLEX OF BACTERIAL TRYPTOPHAN SYNTHASE WITH THE TRANSITION STATE ANALOGUE INHIBITOR 4-(2-HYDROXYPHENYLTHIO)-BUTYLPHOSPHONIC ACID
1FUY 2001-01-17 2.25 CRYSTAL STRUCTURE OF BETAA169L/BETAC170W DOUBLE MUTANT OF TRYPTOPHAN SYNTHASE COMPLEXED WITH 5-FLUORO-INDOLE-PROPANOL PHOSPHATE
1A5S 1999-03-30 2.3 CRYSTAL STRUCTURE OF WILD-TYPE TRYPTOPHAN SYNTHASE COMPLEXED WITH 5-FLUOROINDOLE PROPANOL PHOSPHATE AND L-SER BOUND AS AMINO ACRYLATE TO THE BETA SITE
1C9D 1999-12-29 2.3 CRYSTAL STRUCTURE OF THE COMPLEX OF BACTERIAL TRYPTOPHAN SYNTHASE WITH THE TRANSITION STATE ANALOGUE INHIBITOR 4-(2-HYDROXY-4-FLUOROPHENYLTHIO)-BUTYLPHOSPHONIC ACID
1K7E 2002-07-10 2.3 CRYSTAL STRUCTURE OF WILD-TYPE TRYPTOPHAN SYNTHASE COMPLEXED WITH N-[1H-INDOL-3-YL-ACETYL]GLYCINE ACID
1A50 1999-03-30 2.3 CRYSTAL STRUCTURE OF WILD-TYPE TRYPTOPHAN SYNTHASE COMPLEXED WITH 5-FLUOROINDOLE PROPANOL PHOSPHATE
1C29 2000-01-14 2.3 CRYSTAL STRUCTURE OF THE COMPLEX OF BACTERIAL TRYPTOPHAN SYNTHASE WITH THE TRANSITION STATE ANALOGUE INHIBITOR 4-(2-HYDROXYPHENYLTHIO)-1-BUTENYLPHOSPHONIC ACID
1TTP 1996-03-08 2.3 TRYPTOPHAN SYNTHASE (E.C.4.2.1.20) IN THE PRESENCE OF CESIUM, ROOM TEMPERATURE
1CX9 1999-12-29 2.3 CRYSTAL STRUCTURE OF THE COMPLEX OF BACTERIAL TRYPTOPHAN SYNTHASE WITH THE TRANSITION STATE ANALOGUE INHIBITOR 4-(2-AMINOPHENYLTHIO)-BUTYLPHOSPHONIC ACID
1KFK 2003-10-21 2.4 Crystal structure of Tryptophan Synthase From Salmonella Typhimurium
2TSY 1997-04-01 2.5 CRYSTAL STRUCTURES OF MUTANT (BETAK87T) TRYPTOPHAN SYNTHASE ALPHA2 BETA2 COMPLEX WITH LIGANDS BOUND TO THE ACTIVE SITES OF THE ALPHA AND BETA SUBUNITS REVEAL LIGAND-INDUCED CONFORMATIONAL CHANGES
2DH5 2007-04-24 2.9 Crystal structure of E. coli Holo-TrpB
2DH6 2007-04-24 3.0 Crystal structure of E. coli Apo-TrpB
2WSY 1999-03-30 3.05 CRYSTAL STRUCTURE OF WILD-TYPE TRYPTOPHAN SYNTHASE

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
95.1 Tryptophan synthase alpha chain A9MPY6 TRPA_SALAR
98.9 Tryptophan synthase alpha chain B4TX39 TRPA_SALSV
99.3 Tryptophan synthase alpha chain B5BIC0 TRPA_SALPK
99.3 Tryptophan synthase alpha chain Q5PNM0 TRPA_SALPA
99.3 Tryptophan synthase alpha chain C0Q3N3 TRPA_SALPC
99.3 Tryptophan synthase alpha chain Q57NT2 TRPA_SALCH
99.6 Tryptophan synthase alpha chain Q8Z7E0 TRPA_SALTI
99.6 Tryptophan synthase alpha chain A9MWR3 TRPA_SALPB
99.6 Tryptophan synthase alpha chain B4T6X2 TRPA_SALNS
99.6 Tryptophan synthase alpha chain B4TJK9 TRPA_SALHS
99.6 Tryptophan synthase alpha chain B5R6M4 TRPA_SALG2
99.6 Tryptophan synthase alpha chain B5R3P3 TRPA_SALEP
99.6 Tryptophan synthase alpha chain B5FU65 TRPA_SALDC
99.6 Tryptophan synthase alpha chain B5F4M3 TRPA_SALA4
100.0 Tryptophan synthase alpha chain P00929 TRPA_SALTY
90.1 B Tryptophan synthase alpha chain B2VKT2 TRPB_ERWT9
90.9 B Tryptophan synthase alpha chain Q6D4U0 TRPB_PECAS
91.1 B Tryptophan synthase alpha chain A8GF82 TRPB_SERP5
91.6 B Tryptophan synthase alpha chain C6DGZ5 TRPB_PECCP
93.2 B Tryptophan synthase alpha chain A7MMG1 TRPB_CROS8
92.7 B Tryptophan synthase alpha chain A4WB02 TRPB_ENT38
93.7 B Tryptophan synthase alpha chain A6T7W6 TRPB_KLEP7
93.7 B Tryptophan synthase alpha chain B5XT02 TRPB_KLEP3
96.5 B Tryptophan synthase alpha chain Q31ZV4 TRPB_SHIBS
96.5 B Tryptophan synthase alpha chain B2U0F2 TRPB_SHIB3
96.5 B Tryptophan synthase alpha chain B7N474 TRPB_ECOLU
96.5 B Tryptophan synthase alpha chain Q1RCA6 TRPB_ECOUT
96.5 B Tryptophan synthase alpha chain A1AAN1 TRPB_ECOK1
96.5 B Tryptophan synthase alpha chain B7ML77 TRPB_ECO45
96.5 B Tryptophan synthase alpha chain P0A880 TRPB_SHIFL
96.5 B Tryptophan synthase alpha chain Q0T5D5 TRPB_SHIF8
96.5 B Tryptophan synthase alpha chain B6I9X5 TRPB_ECOSE
96.5 B Tryptophan synthase alpha chain P0A879 TRPB_ECOLI
96.5 B Tryptophan synthase alpha chain B1ITJ4 TRPB_ECOLC
96.5 B Tryptophan synthase alpha chain A7ZZJ7 TRPB_ECOHS
96.5 B Tryptophan synthase alpha chain B1XBL0 TRPB_ECODH
96.5 B Tryptophan synthase alpha chain B7LY17 TRPB_ECO8A
96.5 B Tryptophan synthase alpha chain B7L493 TRPB_ECO55
96.5 B Tryptophan synthase alpha chain A7ZL79 TRPB_ECO24
96.7 B Tryptophan synthase alpha chain Q32GS9 TRPB_SHIDS
96.7 B Tryptophan synthase alpha chain B1LH31 TRPB_ECOSM
96.7 B Tryptophan synthase alpha chain Q8FHV9 TRPB_ECOL6
96.7 B Tryptophan synthase alpha chain Q0TIA9 TRPB_ECOL5
96.7 B Tryptophan synthase alpha chain B7MUA0 TRPB_ECO81
96.7 B Tryptophan synthase alpha chain B7NVN1 TRPB_ECO7I
96.7 B Tryptophan synthase alpha chain B7UR67 TRPB_ECO27
96.7 B Tryptophan synthase alpha chain Q3Z109 TRPB_SHISS
96.7 B Tryptophan synthase alpha chain B5YZP1 TRPB_ECO5E
96.7 B Tryptophan synthase alpha chain Q8X7B6 TRPB_ECO57
97.0 B Tryptophan synthase alpha chain B7LS19 TRPB_ESCF3
96.7 B Tryptophan synthase alpha chain A8AG61 TRPB_CITK8
98.2 B Tryptophan synthase alpha chain A9MPY7 TRPB_SALAR
99.5 B Tryptophan synthase alpha chain Q57NT3 TRPB_SALCH
99.7 B Tryptophan synthase alpha chain P0A2K1 TRPB_SALTY
99.7 B Tryptophan synthase alpha chain P0A2K2 TRPB_SALTI
99.7 B Tryptophan synthase alpha chain B4TX38 TRPB_SALSV
99.7 B Tryptophan synthase alpha chain B5BIC1 TRPB_SALPK
99.7 B Tryptophan synthase alpha chain C0Q3N4 TRPB_SALPC
99.7 B Tryptophan synthase alpha chain A9MWR4 TRPB_SALPB
99.7 B Tryptophan synthase alpha chain Q5PD17 TRPB_SALPA
99.7 B Tryptophan synthase alpha chain B4T6X1 TRPB_SALNS
99.7 B Tryptophan synthase alpha chain B4TJK8 TRPB_SALHS
99.7 B Tryptophan synthase alpha chain B5R6M5 TRPB_SALG2
99.7 B Tryptophan synthase alpha chain B5R3P4 TRPB_SALEP
99.7 B Tryptophan synthase alpha chain B5FU66 TRPB_SALDC
99.7 B Tryptophan synthase alpha chain B5F4M4 TRPB_SALA4