Backbone makes a significant contribution to the electrostatics of α/β‐barrel proteins

Raychaudhuri, Soumya; Younas, Farhan; Karplus, P.A.; Faerman, C. H.; Ripoll, Daniel R.

doi:10.1002/pro.5560060905

Cited by 14 publications

(15 citation statements)

References 43 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many TIM‐barrel enzymes have flexible βα loops that are used to bind substrate and to bury the catalytic site from bulk solvent. Electrostatic calculations have highlighted a common, distinct electrostatic field pattern determined predominantly by the backbone atoms, which generates a positive potential at the C‐terminal end of the barrel near the active site region [41]. This correlates with the known preference of TIM‐barrel folds to bind negatively charged substrates, in particular phosphate‐containing molecules [11].…”

Section: Discussionmentioning

confidence: 94%

The TIM‐barrel fold: a versatile framework for efficient enzymes

Wierenga¹

2001

FEBS Letters

399

381

View full text Add to dashboard Cite

Recent studies on triosephosphate isomerase (TIM)-barrel enzymes highlight the remarkable versatility of the TIMbarrel scaffold. At least 15 distinct enzyme families use this framework to generate the appropriate active site geometry, always at the C-terminal end of the eight parallel L L-strands of the barrel. Sequence and structure comparisons now suggest that many of the TIM-barrel enzymes are evolutionarily related. Common structural properties of TIM-barrel enzymes are discussed. ß

show abstract

Section: Discussionmentioning

confidence: 94%

The TIM‐barrel fold: a versatile framework for efficient enzymes

Wierenga¹

2001

FEBS Letters

399

381

View full text Add to dashboard Cite

show abstract

“…For instance, if a catalytic residue is at the end of a helix, the helix dipole moment may aid in catalysis (34). The active site of all known ␣͞␤ barrel enzymes is at the C-terminal end of the barrel (22), perhaps to take advantage of the distinct electrostatic field formed by the protein backbone of the barrel (35).…”

Section: Resultsmentioning

confidence: 99%

Evolution of an enzyme active site: The structure of a new crystal form of muconate lactonizing enzyme compared with mandelate racemase and enolase

Hasson

Schlichting

Moulai

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Muconate lactonizing enzyme (MLE), a component of the ␤-ketoadipate pathway of Pseudomonas putida, is a member of a family of related enzymes (the ''enolase superfamily'') that catalyze the abstraction of the ␣-proton of a carboxylic acid in the context of different overall reactions. New untwinned crystal forms of MLE were obtained, one of which diffracts to better than 2.0-Å resolution. The packing of the octameric enzyme in this crystal form is unusual, because the asymmetric unit contains three subunits. The structure of MLE presented here contains no bound metal ion, but is very similar to a recently determined Mn 2؉ -bound structure. Thus, absence of the metal ion does not perturb the structure of the active site. The structures of enolase, mandelate racemase, and MLE were superimposed. A comparison of metal ligands suggests that enolase may retain some characteristics of the ancestor of this enzyme family. Comparison of other residues involved in catalysis indicates two unusual patterns of conservation: (i) that the position of catalytic atoms remains constant, although the residues that contain them are located at different points in the protein fold; and (ii) that the positions of catalytic residues in the protein scaffold are conserved, whereas their identities and roles in catalysis vary.

show abstract

“…The positive charge center was calculated by using “positive” residues (arginines and lysines). These titratable residues, aspartate, glutamate, arginine, and lysine, were assumed to be charged, whereas histidine, cysteine, and tyrosine were considered to be neutral 16…”

Section: Methodsmentioning

confidence: 99%

Charge centers and formation of the protein folding core

Torshin

Harrison

2001

Proteins

View full text Add to dashboard Cite

Electrostatic interactions are important for protein folding. At low resolution, the electrostatic field of the whole molecule can be described in terms of charge center(s). To study electrostatic effects, the centers of positive and negative charge were calculated for 20 small proteins of known structure, for which hydrogen exchange cores had been determined experimentally. Two observations seem to be important. First, in all 20 proteins studied 30-100% of the residues forming hydrogen exchange core(s) were clustered around the charge centers. Moreover, in each protein more than half of the core sequences are located near the centers of charge. Second, the general architecture of all-alpha proteins from the set seems to be stabilized by interactions of residues surrounding the charge centers. In most of the alpha-beta proteins, either or both of the centers are located near a pair of consecutive strands, and this is even more characteristic for alpha/Beta and all-beta structures. Consecutive strands are very probable sites of early folding events. These two points lead to the conclusion that charge centers, defined solely from the structure of the folded protein may indicate the location of a protein's hydrogen exchange/folding core. In addition, almost all the proteins contain well-conserved continuous hydrophobic sequences of three or more residues located in the vicinity of the charge centers. These hydrophobic sequences may be primary nucleation sites for protein folding. The results suggest the following scheme for the order of events in folding: local hydrophobic nucleation, electrostatic collapse of the core, global hydrophobic collapse, and slow annealing to the native state. This analysis emphasizes the importance of treating electrostatics during protein-folding simulations.

show abstract

Backbone makes a significant contribution to the electrostatics of α/β‐barrel proteins

Cited by 14 publications

References 43 publications

The TIM‐barrel fold: a versatile framework for efficient enzymes

The TIM‐barrel fold: a versatile framework for efficient enzymes

Evolution of an enzyme active site: The structure of a new crystal form of muconate lactonizing enzyme compared with mandelate racemase and enolase

Charge centers and formation of the protein folding core

Contact Info

Product

Resources

About