Sandbox Reserved 774
From Proteopedia
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=Secondary Structure= | =Secondary Structure= | ||
| - | + | Most of the secondary structure elements of the monomer contribute residues involved in dimer contacts. A large part of the interface is formed by two projections from the core part of the monomer structure. The first projection is formed by the C-terminal end of strand B3, turn B3-B4, and the N-terminal end of strand B4, while the second is formed by strand B7. Together with strands B5 and B6 they form a barrel-like structure containing ten strands in which the component strands of the barrel locked together. Most importantly, strand b7 from each monomer interacts between strands b5 and b6 of the opposite monomer, which also extends the central sheet structure by two strands. | |
| - | Most of the secondary structure elements of the monomer contribute residues in dimer contacts. | + | Also, the two projections interact with residues from helices a1 and a2, turn a1 a2, turn a2 b2, and helices a3 and a4 of the opposite monomer. There are eight beta-strands, four alpha-helices, and ten turns. |
[[Image:Hpa2_Active_Sites.jpg]] | [[Image:Hpa2_Active_Sites.jpg]] | ||
Revision as of 16:25, 30 November 2013
| This Sandbox is Reserved from Sep 25, 2013, through Mar 31, 2014 for use in the course "BCH455/555 Proteins and Molecular Mechanisms" taught by Michael B. Goshe at the North Carolina State University. This reservation includes Sandbox Reserved 299, Sandbox Reserved 300 and Sandbox Reserved 760 through Sandbox Reserved 779. |
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Contents |
Introduction
My protein is Histone Acetyltransferase Hpa2. Hpa2 is a member of the GNAT (Gcn5-related N-acetyltransferases) super-family of enzymes that are found spread out across nature and use acyl-CoA's to acylate their cognate substrates. Histone Acetyltransferase Hpa2 is found in the organism Saccharomyces Cerevisiae, which is more commonly known as Baker's Yeast. In vitro, Hpa2 serves to acetylate histone H3 'Lys-4' and 'Lys-14' and histone H4 'Lys-5' and 'Lys-12.' In solution, Hpa2 forms a dimer, and upon binding with AcCoA forms a tetramer. It is classified as a transferase.
Structure
Has a chain structure with 2.4 A resolution, and 2.9 A resolution with a co-factor (acetyl-CoA). The method used to determine the structure was X-ray crystallography. Sedimentation and crystal structure analysis clearly shows that Hpa2 is dimeric in solution and tetramerizes in the unit crystal. The average B-factor value is 23.9 (main chain) with a 25.4 side chain. The R-factor is 0.19.
Secondary Structure
Most of the secondary structure elements of the monomer contribute residues involved in dimer contacts. A large part of the interface is formed by two projections from the core part of the monomer structure. The first projection is formed by the C-terminal end of strand B3, turn B3-B4, and the N-terminal end of strand B4, while the second is formed by strand B7. Together with strands B5 and B6 they form a barrel-like structure containing ten strands in which the component strands of the barrel locked together. Most importantly, strand b7 from each monomer interacts between strands b5 and b6 of the opposite monomer, which also extends the central sheet structure by two strands. Also, the two projections interact with residues from helices a1 and a2, turn a1 a2, turn a2 b2, and helices a3 and a4 of the opposite monomer. There are eight beta-strands, four alpha-helices, and ten turns.
Description
This structure contains ... alpha helices...
3D Structure
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Mechanism
Protein surfaces near the active site are characterized by a positive electrostatic potential. In each structure there are several multi-chain carbonyl groups without hydrogen bonding partners in the active site. These could act in a proton transfer pathway by helping locate water molecules. Around the acetyl group, there exists a hydrophobic pocket which would stabilize the neutral charge while the substrate is bound to the enzyme once the amino group is deprotonated.
Kinetic Mechanism
The binding of substrates and release of products can be random, fully ordered, or a combination of both. It operates on a Bi-Bi mechanism.
Chemical Mechanism
After the formation of a ternary complex of acetyl-CoA, histone and enzyme, an active site base deprotonates lysin, which allows for direct attack of the N-e-lysine on the carbonyl carbon of acetyl-CoA.
Implications
The analysis of a loss-of-function mutant of the hpa2 gene suggests that the hpa2 affects bacterial proliferation in host plants and a hypersensitive response in nonhost plants. As this is the first of such enzyme activity identified in the Hrp protein family, we speculate that the Hpa2 contributes to the assembly of the TTSS by enlarging gaps in the peptidoglycan meshwork of bacterial cell walls. Hpa2 also plays a role in governing gene expression through its effects on chromatin structure and assembly. Additionally, it affects gene regulation, antibiotic resistance, and hormonal regulation of circadian rhythms.
