Computational Design of New Protein Catalysts

2011 ◽  
pp. 241-266 ◽  
Author(s):  
Gert Kiss ◽  
Scott A. Johnson ◽  
Geoffrey Nosrati ◽  
Nihan Çelebi-Ölçüm ◽  
Seonah Kim ◽  
...  
Keyword(s):  
Computational Design ◽  
New Protein

Computational design of cephradine synthase in a new scaffold identified from structural databases

2017 ◽  
Vol 53 (54) ◽  
pp. 7604-7607 ◽  
Author(s):  
Xiaoqiang Huang ◽  
Jing Xue ◽  
Yushan Zhu
Keyword(s):  
Computational Design ◽  
Protein Scaffold ◽  
Lactam Antibiotic ◽  
Structural Databases ◽  
New Protein

A new protein scaffold was identified and redesigned to catalyze the synthesis of β-lactam antibiotic cephradine.

scholarly journals Computational design of structured loops for new protein functions

2019 ◽  
Vol 400 (3) ◽  
pp. 275-288 ◽  
Author(s):  
Kale Kundert ◽  
Tanja Kortemme
Keyword(s):  
Protein Design ◽  
Protein Function ◽  
Structure Prediction ◽  
Computational Design ◽  
Loop Structure ◽  
Functional Sites ◽  
Loop Design ◽  
Routine Design ◽  
Protein Functions ◽  
New Protein

Abstract The ability to engineer the precise geometries, fine-tuned energetics and subtle dynamics that are characteristic of functional proteins is a major unsolved challenge in the field of computational protein design. In natural proteins, functional sites exhibiting these properties often feature structured loops. However, unlike the elements of secondary structures that comprise idealized protein folds, structured loops have been difficult to design computationally. Addressing this shortcoming in a general way is a necessary first step towards the routine design of protein function. In this perspective, we will describe the progress that has been made on this problem and discuss how recent advances in the field of loop structure prediction can be harnessed and applied to the inverse problem of computational loop design.

scholarly journals Computational design of a modular protein sense-response system

Science ◽  
2019 ◽  
Vol 366 (6468) ◽  
pp. 1024-1028 ◽  
Author(s):  
Anum A. Glasgow ◽  
Yao-Ming Huang ◽  
Daniel J. Mandell ◽  
Michael Thompson ◽  
Ryan Ritterson ◽  
...  
Keyword(s):  
De Novo ◽  
Protein Structures ◽  
Computational Design ◽  
Metabolic Intermediate ◽  
Protein Interfaces ◽  
Substantial Progress ◽  
Valuable Compounds ◽  
Protein Sensors ◽  
New Protein

Sensing and responding to signals is a fundamental ability of living systems, but despite substantial progress in the computational design of new protein structures, there is no general approach for engineering arbitrary new protein sensors. Here, we describe a generalizable computational strategy for designing sensor-actuator proteins by building binding sites de novo into heterodimeric protein-protein interfaces and coupling ligand sensing to modular actuation through split reporters. Using this approach, we designed protein sensors that respond to farnesyl pyrophosphate, a metabolic intermediate in the production of valuable compounds. The sensors are functional in vitro and in cells, and the crystal structure of the engineered binding site closely matches the design model. Our computational design strategy opens broad avenues to link biological outputs to new signals.

scholarly journals Computational design of a modular protein sense/response system

2019 ◽  
Author(s):  
Anum A. Glasgow ◽  
Yao-Ming Huang ◽  
Daniel J. Mandell ◽  
Michael Thompson ◽  
Ryan Ritterson ◽  
...  
Keyword(s):  
De Novo ◽  
Protein Structures ◽  
Computational Design ◽  
Metabolic Intermediate ◽  
Signaling Systems ◽  
Engineering Strategy ◽  
Valuable Compounds ◽  
Protein Sensors ◽  
New Protein

ABSTRACTSensing and responding to signals is a fundamental ability of living systems, but despite remarkable progress in computational design of new protein structures, there is no general approach for engineering arbitrary new protein sensors. Here we describe a generalizable computational strategy for designing sensor/actuator proteins by building binding sites de novo into heterodimeric protein-protein interfaces and coupling ligand sensing to modular actuation via split reporters. Using this approach, we designed protein sensors that respond to farnesyl pyrophosphate, a metabolic intermediate in the production of valuable compounds. The sensors are functional in vitro and in cells, and the crystal structure of the engineered binding site matches the design model with atomic accuracy. Our computational design strategy opens broad avenues to link biological outputs to new signals.One Sentence SummaryAn engineering strategy to design modular synthetic signaling systems that respond to new small molecule inputs.

Direct Molecular Fishing of New Protein Partners for Human Thromboxane Synthase

Acta Naturae ◽  
2017 ◽  
Vol 9 (4) ◽  
pp. 92-100 ◽  
Author(s):  
A. V. Svirid ◽  
◽  
P. V. Ershov ◽  
E. O. Yablokov ◽  
L. A. Kaluzhskiy ◽  
...  
Keyword(s):  
Thromboxane Synthase ◽  
Protein Partners ◽  
Molecular Fishing ◽  
New Protein

TAMM HORSFALL PROTEIN: THE MEN BEHIND THE EPONYM

2019 ◽  
Vol 23 (2) ◽  
pp. 117-119 ◽  
Author(s):  
D. N. Paskalev ◽  
B. T. Galunska ◽  
D. Petkova-Valkova
Keyword(s):  
Viral Replication ◽  
Research Team ◽  
Molecular Mechanisms ◽  
Thick Ascending Limb ◽  
Rockefeller Institute ◽  
The Usa ◽  
Natural Inhibitor ◽  
Simplex Virus ◽  
First Time ◽  
New Protein

Tamm–Horsfall Protein (uromodulin) is named after Igor Tamm and Franc Horsfall Jr who described it for the first time in 1952. It is a glycoprotein, secreted by the cells in the thick ascending limb of the loop of Henle. This protein will perform a number of important pathophysiological functions, including protection against uroinfections, especially caused by E. Сoli, and protection against formation of calcium concernments in the kidney. Igor Tamm (1922-1995) is an outstanding cytologist, virologist and biochemist. He is one of the pioneers in the study of viral replication. He was born in Estonia and died in the USA. In 1964 he was elected for a professorship in Rockefeller Institute for Medical Research, where has been working continuously. Since 1959, he became a head of the virology lab established by his mentor and co-author Franc Horsfall. In the course of studies on the natural inhibitor of viral replication, Tamm and Horsfall isolated and characterized biochemically a new protein named after their names. Franc Lappin Horsfall Jr (1906-1971) was a well-known clinician and virologist with remarkable achievements in internal medicine. He was born and died in the USA. He worked in the Rockefeller Hospital from 1934 to 1960, then in the Center for Cancer Research at the Sloan-Kettering Institute. Here he was a leader of a research team studying the molecular mechanisms of immunity, the effects of chemotherapy with benzimidazole compounds (together with I. Tamm), coxsackie viruses, herpes simplex virus, etc. 

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