Crystallographic Analysis of Active Site Contributions to Regiospecificity in the Diiron Enzyme Toluene 4-Monooxygenase

Biochemistry ◽  
2012 ◽  
Vol 51 (6) ◽  
pp. 1101-1113 ◽  
Author(s):  
Lucas J. Bailey ◽  
Justin F. Acheson ◽  
Jason G. McCoy ◽  
Nathaniel L. Elsen ◽  
George N. Phillips ◽  
...  
Keyword(s):  
Active Site ◽  
Crystallographic Analysis ◽  
Diiron Enzyme

Synthesis, evaluation, and crystallographic analysis of L-371,912: A potent and selective active-site thrombin inhibitor

1997 ◽  
Vol 7 (1) ◽  
pp. 67-72 ◽  
Author(s):  
Terry A. Lyle ◽  
Zhongguo Chen ◽  
Sandra D. Appleby ◽  
Roger M. Freidinger ◽  
Stephen J. Gardell ◽  
...  
Keyword(s):  
Active Site ◽  
Crystallographic Analysis ◽  
Thrombin Inhibitor

scholarly journals Structural Insights into the Molecular Evolution of the Archaeal Exo-β-d-Glucosaminidase

2019 ◽  
Vol 20 (10) ◽  
pp. 2460
Author(s):  
Shouhei Mine ◽  
Masahiro Watanabe
Keyword(s):  
Molecular Evolution ◽  
Primary Structure ◽  
Active Site ◽  
Catalytic Mechanism ◽  
Thermostable Enzyme ◽  
Crystallographic Analysis ◽  
Evolutionary Pathway ◽  
Chitosan Oligosaccharides ◽  
Tim Barrel ◽  
Structural Insights

The archaeal exo-β-d-glucosaminidase (GlmA), a thermostable enzyme belonging to the glycosidase hydrolase (GH) 35 family, hydrolyzes chitosan oligosaccharides into monomer glucosamines. GlmA is a novel enzyme in terms of its primary structure, as it is homologous to both GH35 and GH42 β-galactosidases. The catalytic mechanism of GlmA is not known. Here, we summarize the recent reports on the crystallographic analysis of GlmA. GlmA is a homodimer, with each subunit comprising three distinct domains: a catalytic TIM-barrel domain, an α/β domain, and a β1 domain. Surprisingly, the structure of GlmA presents features common to GH35 and GH42 β-galactosidases, with the domain organization resembling that of GH42 β-galactosidases and the active-site architecture resembling that of GH35 β-galactosidases. Additionally, the GlmA structure also provides critical information about its catalytic mechanism, in particular, on how the enzyme can recognize glucosamine. Finally, we postulate an evolutionary pathway based on the structure of an ancestor GlmA to extant GH35 and GH42 β-galactosidases.

Active site titration of bovine β-trypsin by Nα -(N,N -dimethylcarbamoyl)-α-aza-lysine p -nitrophenyl ester: kinetic and crystallographic analysis

FEBS Letters ◽  
1995 ◽  
Vol 358 (1) ◽  
pp. 53-56 ◽  
Author(s):  
Patrizia Sartori ◽  
Kristina Djinovic Carugo ◽  
Raffaella Ferraccioli ◽  
Gianni Balliano ◽  
Paola Milla ◽  
...  
Keyword(s):  
Active Site ◽  
Crystallographic Analysis ◽  
Nitrophenyl Ester

Structure and specificity of antibody molecules

1975 ◽  
Vol 272 (915) ◽  
pp. 43-51 ◽  
Keyword(s):  
Active Site ◽  
Three Dimensional ◽  
Crystallographic Analysis ◽  
Spatial Proximity ◽  
Three Dimensional Model ◽  
Fab Fragment ◽  
Active Centre ◽  
Myeloma Protein ◽  
Close Spatial Proximity ◽  
Difference Fourier

The structure of the Fab' fragment of a human myeloma protein (IgG1 (λ) New) has been determined by X-ray crystallographic analysis to a nominal resolution of 0.2 nm. Each of the structure subunits corresponding to the variable and to the constant homology regions of the light and heavy polypeptide chains contains two irregular (3-sheets which are roughly parallel to each other and surround a tightly packed interior of hydrophobic side chains. The regions of the hypervariable sequences in the light and heavy chains occur in close spatial proximity at one end of the molecule, defining the active site of IgG New. The role of these hypervariable regions in defining the size and shape of the active site of different immunoglobulins is discussed on the basis of the three-dimensional model of Fab' New. Several ligands that bind to the active centre of IgG New have been used to obtain crystalline ligand-Fab' New complexes which were investigated by difference Fourier maps. These studies are analysed in terms of the biological function and specificity of antibodies.

scholarly journals Catalytic specificity of the Lactobacillus plantarum cystathionine γ-lyase presumed by the crystallographic analysis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yasuyuki Matoba ◽  
Masafumi Noda ◽  
Tomoki Yoshida ◽  
Kosuke Oda ◽  
Yuka Ezumi ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Lactobacillus Plantarum ◽  
Sulfur Atom ◽  
Active Site ◽  
Crystallographic Analysis ◽  
Carboxyl Groups ◽  
Elimination Reaction ◽  
Transsulfuration Pathway ◽  
Lyase Activity ◽  
Major Reaction

Abstract The reverse transsulfuration pathway, which is composed of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGL), plays a role to synthesize l-cysteine using l-serine and the sulfur atom in l-methionine. A plant-derived lactic acid bacterium Lactobacillus plantarum SN35N has been previously found to harbor the gene cluster encoding the CBS- and CGL-like enzymes. In addition, it has been demonstrated that the L. plantarum CBS can synthesize cystathionine from O-acetyl-l-serine and l-homocysteine. The aim of this study is to characterize the enzymatic functions of the L. plantarum CGL. We have found that the enzyme has the high γ-lyase activity toward cystathionine to generate l-cysteine, together with the β-lyase activity toward l-cystine to generate l-cysteine persulfide. By the crystallographic analysis of the inactive CGL K194A mutant complexed with cystathionine, we have found the residues which recognize the distal amino and carboxyl groups of cystathionine or l-cystine. The PLP-bound substrates at the active site may take either the binding pose for the γ- or β-elimination reaction, with the former being the major reaction in the case of cystathionine.

ChemInform Abstract: Synthesis, Evaluation, and Crystallographic Analysis of L-371,912: A Potent and Selective Active-Site Thrombin Inhibitor.

ChemInform ◽  
2010 ◽  
Vol 28 (20) ◽  
pp. no-no
Author(s):  
T. A. LYLE ◽  
Z. CHEN ◽  
S. D. APPLEBY ◽  
R. M. FREIDINGER ◽  
S. J. GARDELL ◽  
...  
Keyword(s):  
Active Site ◽  
Crystallographic Analysis ◽  
Thrombin Inhibitor

scholarly journals Evaluating the Substrate-Envelope Hypothesis: Structural Analysis of Novel HIV-1 Protease Inhibitors Designed To Be Robust against Drug Resistance

2010 ◽  
Vol 84 (10) ◽  
pp. 5368-5378 ◽  
Author(s):  
Madhavi N. L. Nalam ◽  
Akbar Ali ◽  
Michael D. Altman ◽  
G. S. Kiran Kumar Reddy ◽  
Sripriya Chellappan ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Protease Inhibitors ◽  
Active Site ◽  
Crystallographic Analysis ◽  
Van Der Waals Interactions ◽  
Drug Resistant ◽  
Design Strategies ◽  
Resistance Mutations ◽  
Hiv 1 ◽  
Substrate Envelope

ABSTRACT Drug resistance mutations in HIV-1 protease selectively alter inhibitor binding without significantly affecting substrate recognition and cleavage. This alteration in molecular recognition led us to develop the substrate-envelope hypothesis which predicts that HIV-1 protease inhibitors that fit within the overlapping consensus volume of the substrates are less likely to be susceptible to drug-resistant mutations, as a mutation impacting such inhibitors would simultaneously impact the processing of substrates. To evaluate this hypothesis, over 130 HIV-1 protease inhibitors were designed and synthesized using three different approaches with and without substrate-envelope constraints. A subset of 16 representative inhibitors with binding affinities to wild-type protease ranging from 58 nM to 0.8 pM was chosen for crystallographic analysis. The inhibitor-protease complexes revealed that tightly binding inhibitors (at the picomolar level of affinity) appear to “lock” into the protease active site by forming hydrogen bonds to particular active-site residues. Both this hydrogen bonding pattern and subtle variations in protein-ligand van der Waals interactions distinguish nanomolar from picomolar inhibitors. In general, inhibitors that fit within the substrate envelope, regardless of whether they are picomolar or nanomolar, have flatter profiles with respect to drug-resistant protease variants than inhibitors that protrude beyond the substrate envelope; this provides a strong rationale for incorporating substrate-envelope constraints into structure-based design strategies to develop new HIV-1 protease inhibitors.

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