Structural and dynamic basis of acid amido synthetase GH3.1: an investigation of substrate selectivity and major active site access channels

2015 ◽  
Vol 11 (3) ◽  
pp. 809-818 ◽  
Author(s):  
Xue Wang ◽  
Juan Du ◽  
Xiaojun Yao
Keyword(s):  
Active Site ◽  
Substrate Selectivity ◽  
Site Access

Investigation for substrate selectivity and active site access channels of GH3.1, a critical enzyme involved in modulating levels of cellular auxins/IAA.

Structural and Dynamic Basis of Human Cytochrome P450 7B1: A Survey of Substrate Selectivity and Major Active Site Access Channels

2012 ◽  
Vol 19 (2) ◽  
pp. 549-557 ◽  
Author(s):  
Ying-Lu Cui ◽  
Ji-Long Zhang ◽  
Qing-Chuan Zheng ◽  
Rui-Juan Niu ◽  
Yu Xu ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Active Site ◽  
Substrate Selectivity ◽  
Human Cytochrome ◽  
Site Access

Differential Contribution of Active Site Residues in Substrate Recognition Sites 1 and 5 to Cytochrome P450 2C8 Substrate Selectivity and Regioselectivity†

Biochemistry ◽  
2004 ◽  
Vol 43 (24) ◽  
pp. 7834-7842 ◽  
Author(s):  
Oranun Kerdpin ◽  
David J. Elliot ◽  
Sanford L. Boye ◽  
Donald J. Birkett ◽  
Krongtong Yoovathaworn ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Active Site ◽  
Substrate Recognition ◽  
Substrate Selectivity ◽  
Active Site Residues ◽  
Recognition Sites ◽  
Cytochrome P450 2C8 ◽  
Differential Contribution

Rational backbone redesign of a fructosyl peptide oxidase to widen its active site access tunnel

2020 ◽  
Vol 117 (12) ◽  
pp. 3688-3698
Author(s):  
Federica Rigoldi ◽  
Stefano Donini ◽  
Archimede Torretta ◽  
Anna Carbone ◽  
Alberto Redaelli ◽  
...  
Keyword(s):  
Active Site ◽  
Site Access ◽  
Fructosyl Peptide Oxidase

scholarly journals Active-Site Gating Regulates Substrate Selectivity in a Chymotrypsin-Like Serine Protease

2009 ◽  
Vol 389 (3) ◽  
pp. 559-574 ◽  
Author(s):  
Troy A. Johnson ◽  
Jiazhou Qiu ◽  
Andrew G. Plaut ◽  
Todd Holyoak
Keyword(s):  
Serine Protease ◽  
Active Site ◽  
Substrate Selectivity

scholarly journals Structure of theS. aureusPI-Specific Phospholipase C Reveals Modulation of Active Site Access by a Titratable π-Cation Latched Loop

Biochemistry ◽  
2012 ◽  
Vol 51 (12) ◽  
pp. 2579-2587 ◽  
Author(s):  
Rebecca Goldstein ◽  
Jiongjia Cheng ◽  
Boguslaw Stec ◽  
Mary F. Roberts
Keyword(s):  
Phospholipase C ◽  
Active Site ◽  
Site Access

scholarly journals Expression, purification, crystallization and preliminary X-ray diffraction analysis of acylpeptide hydrolase fromDeinococcus radiodurans

2014 ◽  
Vol 70 (9) ◽  
pp. 1292-1295 ◽  
Author(s):  
Venkata Narayana Are ◽  
Biplab Ghosh ◽  
Ashwani Kumar ◽  
Pooja Yadav ◽  
Deepak Bhatnagar ◽  
...  
Keyword(s):  
Active Site ◽  
Mammalian Cells ◽  
Deinococcus Radiodurans ◽  
Structural Information ◽  
Screening Method ◽  
Substrate Selectivity ◽  
Cell Parameters ◽  
Acylpeptide Hydrolase ◽  
Monomeric Structure

Acylpeptide hydrolase (APH; EC 3.4.19.1), which belongs to the S9 family of serine peptidases (MEROPS), catalyzes the removal of anN-acylated amino acid from a blocked peptide. The role of this enzyme in mammalian cells has been suggested to be in the clearance of oxidatively damaged proteins as well as in the degradation of the β-amyloid peptides implicated in Alzheimer's disease. Detailed structural information for the enzyme has been reported from two thermophilic archaea; both of the archaeal APHs share a similar monomeric structure. However, the mechanisms of substrate selectivity and active-site accessibility are totally different and are determined by inter-domain flexibility or the oligomeric structure. An APH homologue from a bacterium,Deinococcus radiodurans(APHdr), has been crystallized using microbatch-under-oil employing the random microseed matrix screening method. The protein crystallized in space groupP21, with unit-cell parametersa= 77.6,b= 189.6,c= 120.4 Å, β = 108.4°. A Matthews coefficient of 2.89 Å3 Da−1corresponds to four monomers, each with a molecular mass of ∼73 kDa, in the asymmetric unit. The APHdr structure will reveal the mechanisms of substrate selectivity and active-site accessibility in the bacterial enzyme. It will also be helpful in elucidating the functional role of this enzyme inD. radiodurans.

scholarly journals Structure of an ancestral mammalian family 1B1 cytochrome P450 with increased thermostability

2020 ◽  
Vol 295 (17) ◽  
pp. 5640-5653 ◽  
Author(s):  
Aaron G. Bart ◽  
Kurt L. Harris ◽  
Elizabeth M. J. Gillam ◽  
Emily E. Scott
Keyword(s):  
Cytochrome P450 ◽  
Active Site ◽  
Substrate Selectivity ◽  
Cytochrome P450 Enzymes ◽  
Drug Molecules ◽  
Structural Evaluation ◽  
Aromatic Interactions ◽  
Open Conformation ◽  
17Β Estradiol ◽  
Variable Substrate

Mammalian cytochrome P450 enzymes often metabolize many pharmaceuticals and other xenobiotics, a feature that is valuable in a biotechnology setting. However, extant P450 enzymes are typically relatively unstable, with T50 values of ∼30–40 °C. Reconstructed ancestral cytochrome P450 enzymes tend to have variable substrate selectivity compared with related extant forms, but they also have higher thermostability and therefore may be excellent tools for commercial biosynthesis of important intermediates, final drug molecules, or drug metabolites. The mammalian ancestor of the cytochrome P450 1B subfamily was herein characterized structurally and functionally, revealing differences from the extant human CYP1B1 in ligand binding, metabolism, and potential molecular contributors to its thermostability. Whereas extant human CYP1B1 has one molecule of α-naphthoflavone in a closed active site, we observed that subtle amino acid substitutions outside the active site in the ancestor CYP1B enzyme yielded an open active site with four ligand copies. A structure of the ancestor with 17β-estradiol revealed only one molecule in the active site, which still had the same open conformation. Detailed comparisons between the extant and ancestor forms revealed increases in electrostatic and aromatic interactions between distinct secondary structure elements in the ancestral forms that may contribute to their thermostability. To the best of our knowledge, this represents the first structural evaluation of a reconstructed ancestral cytochrome P450, revealing key features that appear to contribute to its thermostability.

scholarly journals Structural Basis for Broad Substrate Selectivity of Alcohol Dehydrogenase YjgB from Escherichia coli

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2404
Author(s):  
Giang Thu Nguyen ◽  
Yeon-Gil Kim ◽  
Jae-Woo Ahn ◽  
Jeong Ho Chang
Keyword(s):  
Escherichia Coli ◽  
Active Site ◽  
Nicotinamide Adenine Dinucleotide ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Docking Simulation ◽  
Structural Basis ◽  
Aliphatic Chain ◽  
Substrate Selectivity ◽  
Hydrophobic Pocket ◽  
Simulation Data

In metabolic engineering and synthetic biology fields, there have been efforts to produce variable bioalcohol fuels, such as isobutanol and 2-phenylethanol, in order to meet industrial demands. YjgB is an aldehyde dehydrogenase from Escherichia coli that shows nicotinamide adenine dinucleotide phosphate (NADP)-dependent broad selectivity for aldehyde derivatives with an aromatic ring or small aliphatic chain. This could contribute to the design of industrial synthetic pathways. We determined the crystal structures of YjgB for both its apo-form and NADP-complexed form at resolutions of 1.55 and 2.00 Å, respectively, in order to understand the mechanism of broad substrate selectivity. The hydrophobic pocket of the active site and the nicotinamide ring of NADP(H) are both involved in conferring its broad specificity toward aldehyde substrates. In addition, based on docking-simulation data, we inferred that π–π stacking between substrates and aromatic side chains might play a crucial role in recognizing substrates. Our structural analysis of YjgB might provide insights into establishing frameworks to understand its broad substrate specificity and develop engineered enzymes for industrial biofuel synthesis.

scholarly journals Halogen−π Interactions in the Cytochrome P450 Active Site: Structural Insights into Human CYP2B6 Substrate Selectivity

2017 ◽  
Vol 12 (5) ◽  
pp. 1204-1210 ◽  
Author(s):  
Manish B. Shah ◽  
Jingbao Liu ◽  
Qinghai Zhang ◽  
C. David Stout ◽  
James R. Halpert
Keyword(s):  
Cytochrome P450 ◽  
Active Site ◽  
Substrate Selectivity ◽  
Π Interactions ◽  
Structural Insights
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