Structural modeling and biochemical studies reveal insights into the molecular basis of the recognition ofβ-2-microglobulin by antibody BBM.1

2009 ◽  
Vol 22 (6) ◽  
pp. 465-473 ◽  
Author(s):  
Jiamu Du ◽  
Hui Yang ◽  
Baozhen Peng ◽  
Jianping Ding
Keyword(s):  
Molecular Basis ◽  
Structural Modeling ◽  
Biochemical Studies

scholarly journals The structure of the colorectal cancer-associated enzyme GalNAc-T12 reveals how nonconserved residues dictate its function

2019 ◽  
Vol 116 (41) ◽  
pp. 20404-20410 ◽  
Author(s):  
Amy J. Fernandez ◽  
Earnest James Paul Daniel ◽  
Sai Pooja Mahajan ◽  
Jeffrey J. Gray ◽  
Thomas A. Gerken ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Basis ◽  
Catalytic Domain ◽  
Binding Pocket ◽  
Substrate Selectivity ◽  
Peptide Substrate ◽  
X Ray ◽  
Biochemical Studies ◽  
Cancer Mutations ◽  
Insight Into

Polypeptide N-acetylgalactosaminyl transferases (GalNAc-Ts) initiate mucin type O-glycosylation by catalyzing the transfer of N-acetylgalactosamine (GalNAc) to Ser or Thr on a protein substrate. Inactive and partially active variants of the isoenzyme GalNAc-T12 are present in subsets of patients with colorectal cancer, and several of these variants alter nonconserved residues with unknown functions. While previous biochemical studies have demonstrated that GalNAc-T12 selects for peptide and glycopeptide substrates through unique interactions with its catalytic and lectin domains, the molecular basis for this distinct substrate selectivity remains elusive. Here we examine the molecular basis of the activity and substrate selectivity of GalNAc-T12. The X-ray crystal structure of GalNAc-T12 in complex with a di-glycosylated peptide substrate reveals how a nonconserved GalNAc binding pocket in the GalNAc-T12 catalytic domain dictates its unique substrate selectivity. In addition, the structure provides insight into how colorectal cancer mutations disrupt the activity of GalNAc-T12 and illustrates how the rules dictating GalNAc-T12 function are distinct from those for other GalNAc-Ts.

scholarly journals Molecular basis of barley quality

2003 ◽  
Vol 54 (12) ◽  
pp. 1081 ◽  
Author(s):  
G. P. Fox ◽  
J. F. Panozzo ◽  
C. D. Li ◽  
R. C. M. Lance ◽  
P. A. Inkerman ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Genetic Basis ◽  
Grain Quality ◽  
Animal Feed ◽  
Molecular Genetic ◽  
Malting Quality ◽  
Limited Success ◽  
Biochemical Studies ◽  
Definition Of

The quality of barley for the range of end uses from animal feed to brewing is determined by many genes, making the breeding of new barley varieties difficult. Understanding of the molecular basis of barley quality has been advanced by biochemical studies. More recently, molecular genetic tools are allowing the analysis of the biochemical factors contributing to grain quality. Many genetic loci influencing key quality attributes have been identified by gene mapping. Limited success has been reported in using this information to select for quantitative trait loci for these quality traits in plant breeding. Genomic techniques allowing more detailed analysis of variations in the barley genome in relation to quality promise to extend significantly the value of molecular genetic approaches to barley quality improvement. Definition of the genetic basis of malting quality requires the identification of the genes involved in germination and endosperm modification. Feed quality remains difficult to define. Recent advances are likely to accelerate the rate of discovery, providing new options for analysis of barley quality.

scholarly journals Cell-cycle dependent phosphorylation of yeast pericentrin regulates γ-TuSC-mediated microtubule nucleation

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Tien-chen Lin ◽  
Annett Neuner ◽  
Yvonne T Schlosser ◽  
Annette ND Scharf ◽  
Lisa Weber ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Molecular Basis ◽  
Dependent Manner ◽  
Microtubule Nucleation ◽  
Biochemical Studies ◽  
N Terminus ◽  
Complex Receptor ◽  
A Cell ◽  
Cycle Dependent ◽  
Receptor Family

Budding yeast Spc110, a member of γ-tubulin complex receptor family (γ-TuCR), recruits γ-tubulin complexes to microtubule (MT) organizing centers (MTOCs). Biochemical studies suggest that Spc110 facilitates higher-order γ-tubulin complex assembly (<xref ref-type="bibr" rid="bib45">Kollman et al., 2010</xref>). Nevertheless the molecular basis for this activity and the regulation are unclear. Here we show that Spc110 phosphorylated by Mps1 and Cdk1 activates γ-TuSC oligomerization and MT nucleation in a cell cycle dependent manner. Interaction between the N-terminus of the γ-TuSC subunit Spc98 and Spc110 is important for this activity. Besides the conserved CM1 motif in γ-TuCRs (<xref ref-type="bibr" rid="bib65">Sawin et al., 2004</xref>), a second motif that we named Spc110/Pcp1 motif (SPM) is also important for MT nucleation. The activating Mps1 and Cdk1 sites lie between SPM and CM1 motifs. Most organisms have both SPM-CM1 (Spc110/Pcp1/PCNT) and CM1-only (Spc72/Mto1/Cnn/CDK5RAP2/myomegalin) types of γ-TuCRs. The two types of γ-TuCRs contain distinct but conserved C-terminal MTOC targeting domains.

scholarly journals Structural and biochemical studies define Nudt12 as a new class of RNA deNADding enzyme in mammalian cells

2018 ◽  
Author(s):  
Ewa Grudzien-Nogalska ◽  
Yixuan Wu ◽  
Xinfu Jiao ◽  
Huijuan Cui ◽  
Ronald P. Hart ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Molecular Basis ◽  
Mammalian Cells ◽  
Metabolic Stress ◽  
Cellular Metabolism ◽  
New Class ◽  
Mrna Targets ◽  
Biochemical Studies ◽  
Cellular Energetics ◽  
In Cells

ABSTRACTWe recently demonstrated mammalian cells harbor NAD-capped mRNAs that are hydrolyzed by the DXO deNADding enzyme. Here we report the Nudix protein Nudt12 is a second mammalian deNADding enzyme structurally and mechanistically distinct from DXO and targets different RNAs. Crystal structure of mouse Nudt12 in complex with the deNADding product AMP and three Mg2+ ions at 1.6 Å resolution provides exquisite insights into the molecular basis of the deNADding activity within the NAD pyrophosphate. Disruption of the Nudt12 gene stabilizes transfected NAD-capped RNA in cells and its endogenous NAD-capped mRNA targets are enriched in those encoding proteins involved in cellular energetics. Furthermore, exposure of cells to metabolic stress manifests changes in NAD-capped RNA levels indicating an association between NAD-capped RNAs and cellular metabolism. Lastly, we show that the bacterial RppH protein also possesses deNADding activity toward NAD-capped RNA but not free NAD, revealing a third class of deNADding enzymes.

scholarly journals Molecular basis for catabolism of the abundant metabolite trans-4-hydroxy-L-proline by a microbial glycyl radical enzyme

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Lindsey RF Backman ◽  
Yolanda Y Huang ◽  
Mary C Andorfer ◽  
Brian Gold ◽  
Ronald T Raines ◽  
...  
Keyword(s):  
Active Site ◽  
Metabolic Pathways ◽  
Molecular Basis ◽  
Radical Mechanism ◽  
Human Gut ◽  
Clostridioides Difficile ◽  
Glycyl Radical ◽  
Biochemical Studies ◽  
Glycyl Radical Enzyme ◽  
Insight Into

The glycyl radical enzyme (GRE) superfamily utilizes a glycyl radical cofactor to catalyze difficult chemical reactions in a variety of anaerobic microbial metabolic pathways. Recently, a GRE, trans-4-hydroxy-L-proline (Hyp) dehydratase (HypD), was discovered that catalyzes the dehydration of Hyp to (S)-Δ1-pyrroline-5-carboxylic acid (P5C). This enzyme is abundant in the human gut microbiome and also present in prominent bacterial pathogens. However, we lack an understanding of how HypD performs its unusual chemistry. Here, we have solved the crystal structure of HypD from the pathogen Clostridioides difficile with Hyp bound in the active site. Biochemical studies have led to the identification of key catalytic residues and have provided insight into the radical mechanism of Hyp dehydration.

scholarly journals The fox Operon from Rhodobacter Strain SW2 Promotes Phototrophic Fe(II) Oxidation in Rhodobacter capsulatus SB1003

2006 ◽  
Vol 189 (5) ◽  
pp. 1774-1782 ◽  
Author(s):  
Laura R. Croal ◽  
Yongqin Jiao ◽  
Dianne K. Newman
Keyword(s):  
Molecular Basis ◽  
Rhodobacter Capsulatus ◽  
Maximal Activity ◽  
Pyrroloquinoline Quinone ◽  
Oxygenic Photosynthesis ◽  
Transport Function ◽  
Significant Similarity ◽  
Oxidation Activity ◽  
Biochemical Studies ◽  
And Function

ABSTRACT Anoxygenic photosynthesis based on Fe(II) is thought to be one of the most ancient forms of metabolism and is hypothesized to represent a transition step in the evolution of oxygenic photosynthesis. However, little is known about the molecular basis of this process because, until recently (Y. Jiao and D. K. Newman, J. Bacteriol. 189:1765-1773, 2007), most phototrophic Fe(II)-oxidizing bacteria have been genetically intractable. In this study, we circumvented this problem by taking a heterologous-complementation approach to identify a three-gene operon (the foxEYZ operon) from Rhodobacter sp. strain SW2 that confers enhanced light-dependent Fe(II) oxidation activity when expressed in its genetically tractable relative Rhodobacter capsulatus SB1003. The first gene in this operon, foxE, encodes a c-type cytochrome with no significant similarity to other known proteins. Expression of foxE alone confers significant light-dependent Fe(II) oxidation activity on SB1003, but maximal activity is achieved when foxE is expressed with the two downstream genes foxY and foxZ. In SW2, the foxE and foxY genes are cotranscribed in the presence of Fe(II) and/or hydrogen, with foxZ being transcribed only in the presence of Fe(II). Sequence analysis predicts that foxY encodes a protein containing the redox cofactor pyrroloquinoline quinone and that foxZ encodes a protein with a transport function. Future biochemical studies will permit the localization and function of the Fox proteins in SW2 to be determined.

scholarly journals Structural and Biochemical Studies of the Hedamycin Type II Polyketide Ketoreductase (HedKR): Molecular Basis of Stereo- and Regiospecificities

Biochemistry ◽  
2011 ◽  
Vol 50 (34) ◽  
pp. 7426-7439 ◽  
Author(s):  
Pouya Javidpour ◽  
Abhirup Das ◽  
Chaitan Khosla ◽  
Shiou-Chuan Tsai
Keyword(s):  
Molecular Basis ◽  
Type Ii ◽  
Biochemical Studies
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