3D macromolecule..

35/99/170-loops of FXa in SGT

Authors:	Page, M.J., Di Cera, E.
Release Date:	2010-06-02	Classification:	Hydrolase
Experiment:	X-RAY DIFFRACTION with resolution of 2.10 Å
Compound:	1 Polymer 3 Ligands Image Identifier Name Formula ')" onmouseout="UnTip()" width="50px;"> ACT ACETATE ION C2 H3 O2 ')" onmouseout="UnTip()" width="50px;"> CA CALCIUM ION Ca ')" onmouseout="UnTip()" width="50px;"> SO4 SULFATE ION O4 S
Citation:	Combinatorial Enzyme Design Probes Allostery and Cooperativity in the Trypsin Fold. (2010) J.Mol.Biol. 399: 306-319
Molecule of the Month:	Thrombin, Trypsin, Serpins, Tissue Factor, Fibrin

Combinatorial enzyme design probes allostery and cooperativity in the trypsin fold.

Page, M.J., Di Cera, E.

Journal: (2010) J.Mol.Biol. 399: 306-319

PubMed: 20399789
DOI: 10.1016/j.jmb.2010.04.024
Search Related Articles in PubMed

PubMed Abstract:

Converting one enzyme into another is challenging due to the uneven distribution of important amino acids for function in both protein sequence and structure. We report a strategy for protein engineering allowing an organized mixing and matching of genetic material... [ Read More & Search PubMed Abstracts ]

Converting one enzyme into another is challenging due to the uneven distribution of important amino acids for function in both protein sequence and structure. We report a strategy for protein engineering allowing an organized mixing and matching of genetic material that leverages lower throughput with increased quality of screens. Our approach successfully tested the contribution of each surface-exposed loop in the trypsin fold alone and the cooperativity of their combinations towards building the substrate selectivity and Na(+)-dependent allosteric activation of the protease domain of human coagulation factor Xa into a bacterial trypsin. As the created proteases lack additional protein domains and protein co-factor activation mechanism requisite for the complexity of blood coagulation, they are stepping-stones towards further understanding and engineering of artificial clotting factors.

Keywords:


Related Structures:
Primary Citation of: 3I77 3I78

Organizational Affiliation:
Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.

Classification:	Hydrolase
Structure Weight:	24396.34

Molecule:	Trypsin
Polymer:	1	Type:	polypeptide(L)	Length:	230
Chains:	A
EC#:	3.4.21.4
Mutation:	19 substitutions in the 35, 99 and 170-loops
Other Details:	35/99/170-loops of FXa in SGT

Source

Polymer: 1
Scientific Name:	Streptomyces griseus		Expression System:	Bacillus subtilis

Authors: Page, M.J., Di Cera, E. Deposition: 2009-07-08 Release: 2010-06-02

Method: X-RAY DIFFRACTION
Experimental Data:EDS

Resolution[Å]:	2.10
R-Value:	0.164 (obs.)
R-Free:	0.195
Space Group:	I 4 2 2

Unit Cell:
	Length [Å]	Angles [°]
	a = 138.35	α = 90.00
	b = 138.35	β = 90.00
	c = 81.40	γ = 90.

Molecule of the Month Features:

• Thrombin
• Trypsin
• Serpins
• Tissue Factor
• Fibrin

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