Effects of large-scale amino acid substitution in the polypeptide tether connecting the heme and molybdenum domains on catalysis in human sulfite oxidase

Metallomics ◽  
2010 ◽  
Vol 2 (11) ◽  
pp. 766 ◽  
Author(s):  
Kayunta Johnson-Winters ◽  
Anna R. Nordstrom ◽  
Amanda C. Davis ◽  
Gordon Tollin ◽  
John H. Enemark
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Large Scale ◽  
Sulfite Oxidase ◽  
Human Sulfite Oxidase

Identification of HLA Allele Mismatch Combinations and Amino Acid Substitution Positions Associated with GVL Effect after Unrelated HSCT: Analysis from the Japan Marrow Donor Program.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 44-44 ◽  
Author(s):  
Takakazu Kawase ◽  
Keitaro Matsuo ◽  
Koichi Kashiwase ◽  
Hidetoshi Inoko ◽  
Hiroh Saji ◽  
...  
Keyword(s):  
Amino Acid ◽  
High Risk ◽  
Relapse Rate ◽  
Amino Acid Substitution ◽  
Large Scale ◽  
Acute Gvhd ◽  
Hematopoietic Stem ◽  
Specific Amino Acid ◽  
Specific Amino Acid Substitution ◽  
Reduce Relapse Rate

Abstract Graft-versus-leukemia (GVL) effect is considered to reduce relapse rate due to eradication of residual leukemia cells after allogeneic hematopoietic stem cell transplantation (HSCT). Segregation it from graft-versus-host disease (GVHD) has been main issue clinically. We recently clarified 16 high-risk HLA mismatch combinations and eight high-risk specific amino acid substitution positions for severe acute GVHD in six HLA loci. In the current study, we clarified HLA allele mismatch combinations and amino acid substitution positions associated with GVL effect. Consecutive 4643 patients transplanted for hematological malignancy (ALL, AML, CML, MDS, MM and ML) with T cell replete marrow from a serologically HLA-A, -B and -DR antigen-matched donor through Japan Marrow Donor Program were registered in this cohort study. All HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 alleles were retrospectively typed. The effect of HLA locus mismatch in allele level, the HLA allele mismatch combinations in HLA six loci and amino acid substitution positions on reduced relapse rate was analyzed using a multivariable competing risk regression model. As results (1) Mismatches of HLA-C (Odds ratio (OR)=0.69; p<0.0001) and HLA-DPB1 (OR=0.78; p<0.0001) were strongly reduced leukemia relapse, and HLA-A (OR=0.99; p=0.9), HLA-B (OR=0.98; p=0.91), HLA-DRB1 (OR=0.93; p=0.54) and HLA-DQB1 (OR=1.06; p=0.54) were not. (2) Total 10 HLA mismatch combinations were significantly associated with GVL effect; four in HLA-C allele (donor Cw*0303- patient Cw*1502 (n=25) OR=0.23, Cw*0102-Cw*1402 (n=16) OR=0, Cw*0801-Cw*0102 (n=10) OR=0 and Cw*1402-Cw*0304 (n=23) OR=0), six in HLA-DPB1 allele (DP*0402-DP*0201 (n=66) OR=0.41,?DP*0501-DP*0201 (n=351) OR=0.7,?DP*0501-DP*0401 (n=53) OR=0.45,?DP*0501-DP*0402?(n=121) OR=0.59, DP*0901-DP*0201 (n=50) OR=0.38 and DP*1301-DP*0201 (n=21) OR=0), but none in HLA-A, -B, -DRB1 and -DQB1 allele. Except two of four combinations in HLA-C, the other two in HLA-C and all six in HLA-DPB1 were different from high-risk one for severe acute GVHD. (3) Specific amino acid substitution at positions 9, 99, 156 in HLA-C molecule was elucidated as significant factors responsible for GVL effect and one of three was different from substitutions responsible for severe acute GVHD. As for HLA-DPB1, no significant association between the positions of specific amino acid substitution and GVL were found. In conclusion, large scale comprehensive analysis made it possible to identify 4 HLA-C and 6 HLA-DPB1 mismatch combinations responsible for GVL effects, some of which are different from one responsible for acute GVHD. Responsible amino acid substitutions on specific position were also elucidated in HLA-C, but not in HLA-DPB1. These findings suggest that donor selection according to these results could segregate GVL from acute GVHD, therefore these strategies might be beneficial for the selection of suitable donor for HSCT. And that, we speculate that the molecular base of GVL caused by the HLA-DPB1 mismatch might be different from that in HLA-C.

scholarly journals The neutrophil alloantigen HNA-3a (5b) is located on choline transporter-like protein 2 and appears to be encoded by an R>Q154 amino acid substitution

Blood ◽  
2010 ◽  
Vol 115 (10) ◽  
pp. 2073-2076 ◽  
Author(s):  
Brian R. Curtis ◽  
Nancy J. Cox ◽  
Mia J. Sullivan ◽  
Anuar Konkashbaev ◽  
Krista Bowens ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Amino Acid ◽  
Lung Injury ◽  
Amino Acid Substitution ◽  
Large Scale ◽  
Spectrometric Analysis ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Choline Transporter ◽  
Specific Antibodies

Abstract The molecular basis of the HNA-3a/b (5b/a) leukocyte antigen system has not yet been defined despite evidence that HNA-3a–specific antibodies are particularly prone to cause severe, often fatal, transfusion-related lung injury. We used genome-wide single nucleotide polymorphism scanning and sequencing of DNA from persons of different HNA-3a/b phenotypes to identify a single single nucleotide polymorphism in exon 7 of the CLT2 gene (SLC44A2) that predicts an amino acid substitution in the first extracellular loop of choline transporter-like protein 2, a member of the choline transporter-like protein family of membrane glycoproteins, and correlates perfectly with HNA-3a/b phenotypes (R154 encodes HNA-3a; Q154 encodes HNA-3b). Mass spectrometric analysis of proteins immunoprecipitated from leukocytes by anti–HNA-3a provided direct evidence that anti–HNA-3a recognizes choline transporter-like protein 2. These findings will enable large-scale genotyping for HNA-3a/b to identify blood donors at risk to have HNA-3a–specific antibodies and should facilitate development of practical methods to detect such antibodies and prevent transfusion-related lung injury.

Hubsm: A Novel Amino Acid Substitution Matrix for Comparing Hub Proteins

2017 ◽  
Vol 7 (8) ◽  
pp. 212
Author(s):  
Renganayaki G. ◽  
Achuthsankar S. Nair
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Low Complexity ◽  
Database Search ◽  
Substitution Matrix ◽  
Compositional Bias ◽  
Sequence Alignments ◽  
Amino Acid Substitution Matrix ◽  
Alignment Algorithms ◽  
Hub Proteins

Sequence alignment algorithms and  database search methods use BLOSUM and PAM substitution matrices constructed from general proteins. These de facto matrices are not optimal to align sequences accurately, for the proteins with markedly different compositional bias in the amino acid.   In this work, a new amino acid substitution matrix is calculated for the disorder and low complexity rich region of Hub proteins, based on residue characteristics. Insights into the amino acid background frequencies and the substitution scores obtained from the Hubsm unveils the  residue substitution patterns which differs from commonly used scoring matrices .When comparing the Hub protein sequences for detecting homologs,  the use of this Hubsm matrix yields better results than PAM and BLOSUM matrices. Usage of Hubsm matrix can be optimal in database search and for the construction of more accurate sequence alignments of Hub proteins.

scholarly journals A large compressibility change of protein induced by a single amino acid substitution

1996 ◽  
Vol 5 (3) ◽  
pp. 542-545 ◽  
Author(s):  
Kunihiko Gekko ◽  
Youjiro Tamura ◽  
Eiji Ohmae ◽  
Hideyuki Hayashi ◽  
Hiroyuki Kagamiyama ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Single Amino Acid Substitution ◽  
Single Amino Acid

Identification of a Functional Domain Within the Essential Core of Histone H3 That Is Required for Telomeric and HM Silencing in Saccharomyces cerevisiae

Genetics ◽  
2003 ◽  
Vol 163 (1) ◽  
pp. 447-452 ◽  
Author(s):  
Jeffrey S Thompson ◽  
Marilyn L Snow ◽  
Summer Giles ◽  
Leslie E McPherson ◽  
Michael Grunstein
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acid ◽  
Amino Acid Substitution ◽  
Histone H3 ◽  
Single Amino Acid ◽  
Functional Domain ◽  
Partial Loss ◽  
Histone Fold ◽  
Gal1 Promoter ◽  
Substitution Mutations

Abstract Fourteen novel single-amino-acid substitution mutations in histone H3 that disrupt telomeric silencing in Saccharomyces cerevisiae were identified, 10 of which are clustered within the α1 helix and L1 loop of the essential histone fold. Several of these mutations cause derepression of silent mating locus HML, and an additional subset cause partial loss of basal repression at the GAL1 promoter. Our results identify a new domain within the essential core of histone H3 that is required for heterochromatin-mediated silencing.

Sign in / Sign up

Export Citation Format

Share Document