Molecular characterization of novel pyridoxal-5'-phosphate-dependent enzymes from the human microbiome

Nicholas M. Fleischman, Debanu Das, Abhinav Kumar, Qingping Xu, Hsiu Ju Chiu, Lukasz Jaroszewski, Mark W. Knuth, Heath E. Klock, Mitchell D. Miller, Marc André Elsliger, Adam Godzik, Scott A. Lesley, Ashley M. Deacon, Ian A. Wilson, Michael D. Toney

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Pyridoxal-5'-phosphate or PLP, the active form of vitamin B6, is a highly versatile cofactor that participates in a large number of mechanistically diverse enzymatic reactions in basic metabolism. PLP-dependent enzymes account for ∼1.5% of most prokaryotic genomes and are estimated to be involved in ∼4% of all catalytic reactions, making this an important class of enzymes. Here, we structurally and functionally characterize three novel PLP-dependent enzymes from bacteria in the human microbiome: Two are from Eubacterium rectale, a dominant, nonpathogenic, fecal, Gram-positive bacteria, and the third is from Porphyromonas gingivalis, which plays a major role in human periodontal disease. All adopt the Type I PLP-dependent enzyme fold and structure-guided biochemical analysis enabled functional assignments as tryptophan, aromatic, and probable phosphoserine aminotransferases.

Original languageEnglish (US)
Pages (from-to)1060-1076
Number of pages17
JournalProtein Science
Volume23
Issue number8
DOIs
StatePublished - 2014

Fingerprint

Pyridoxal Phosphate
Microbiota
phosphoserine aminotransferase
Enzymes
Bacteria
Eubacterium
Porphyromonas gingivalis
Functional analysis
Vitamin B 6
Gram-Positive Bacteria
Periodontal Diseases
Metabolism
Tryptophan
Genes
Genome

Keywords

  • Biochemical characterization
  • Crystal structure
  • Human microbiome
  • PLP-dependent enzymes
  • Protein structure initiative
  • Structural genomics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Fleischman, N. M., Das, D., Kumar, A., Xu, Q., Chiu, H. J., Jaroszewski, L., ... Toney, M. D. (2014). Molecular characterization of novel pyridoxal-5'-phosphate-dependent enzymes from the human microbiome. Protein Science, 23(8), 1060-1076. https://doi.org/10.1002/pro.2493

Molecular characterization of novel pyridoxal-5'-phosphate-dependent enzymes from the human microbiome. / Fleischman, Nicholas M.; Das, Debanu; Kumar, Abhinav; Xu, Qingping; Chiu, Hsiu Ju; Jaroszewski, Lukasz; Knuth, Mark W.; Klock, Heath E.; Miller, Mitchell D.; Elsliger, Marc André; Godzik, Adam; Lesley, Scott A.; Deacon, Ashley M.; Wilson, Ian A.; Toney, Michael D.

In: Protein Science, Vol. 23, No. 8, 2014, p. 1060-1076.

Research output: Contribution to journalArticle

Fleischman, NM, Das, D, Kumar, A, Xu, Q, Chiu, HJ, Jaroszewski, L, Knuth, MW, Klock, HE, Miller, MD, Elsliger, MA, Godzik, A, Lesley, SA, Deacon, AM, Wilson, IA & Toney, MD 2014, 'Molecular characterization of novel pyridoxal-5'-phosphate-dependent enzymes from the human microbiome', Protein Science, vol. 23, no. 8, pp. 1060-1076. https://doi.org/10.1002/pro.2493
Fleischman, Nicholas M. ; Das, Debanu ; Kumar, Abhinav ; Xu, Qingping ; Chiu, Hsiu Ju ; Jaroszewski, Lukasz ; Knuth, Mark W. ; Klock, Heath E. ; Miller, Mitchell D. ; Elsliger, Marc André ; Godzik, Adam ; Lesley, Scott A. ; Deacon, Ashley M. ; Wilson, Ian A. ; Toney, Michael D. / Molecular characterization of novel pyridoxal-5'-phosphate-dependent enzymes from the human microbiome. In: Protein Science. 2014 ; Vol. 23, No. 8. pp. 1060-1076.
@article{5f87ee074c374457be485003094e1868,
title = "Molecular characterization of novel pyridoxal-5'-phosphate-dependent enzymes from the human microbiome",
abstract = "Pyridoxal-5'-phosphate or PLP, the active form of vitamin B6, is a highly versatile cofactor that participates in a large number of mechanistically diverse enzymatic reactions in basic metabolism. PLP-dependent enzymes account for ∼1.5{\%} of most prokaryotic genomes and are estimated to be involved in ∼4{\%} of all catalytic reactions, making this an important class of enzymes. Here, we structurally and functionally characterize three novel PLP-dependent enzymes from bacteria in the human microbiome: Two are from Eubacterium rectale, a dominant, nonpathogenic, fecal, Gram-positive bacteria, and the third is from Porphyromonas gingivalis, which plays a major role in human periodontal disease. All adopt the Type I PLP-dependent enzyme fold and structure-guided biochemical analysis enabled functional assignments as tryptophan, aromatic, and probable phosphoserine aminotransferases.",
keywords = "Biochemical characterization, Crystal structure, Human microbiome, PLP-dependent enzymes, Protein structure initiative, Structural genomics",
author = "Fleischman, {Nicholas M.} and Debanu Das and Abhinav Kumar and Qingping Xu and Chiu, {Hsiu Ju} and Lukasz Jaroszewski and Knuth, {Mark W.} and Klock, {Heath E.} and Miller, {Mitchell D.} and Elsliger, {Marc Andr{\'e}} and Adam Godzik and Lesley, {Scott A.} and Deacon, {Ashley M.} and Wilson, {Ian A.} and Toney, {Michael D.}",
year = "2014",
doi = "10.1002/pro.2493",
language = "English (US)",
volume = "23",
pages = "1060--1076",
journal = "Protein Science",
issn = "0961-8368",
publisher = "Cold Spring Harbor Laboratory Press",
number = "8",

}

TY - JOUR

T1 - Molecular characterization of novel pyridoxal-5'-phosphate-dependent enzymes from the human microbiome

AU - Fleischman, Nicholas M.

AU - Das, Debanu

AU - Kumar, Abhinav

AU - Xu, Qingping

AU - Chiu, Hsiu Ju

AU - Jaroszewski, Lukasz

AU - Knuth, Mark W.

AU - Klock, Heath E.

AU - Miller, Mitchell D.

AU - Elsliger, Marc André

AU - Godzik, Adam

AU - Lesley, Scott A.

AU - Deacon, Ashley M.

AU - Wilson, Ian A.

AU - Toney, Michael D.

PY - 2014

Y1 - 2014

N2 - Pyridoxal-5'-phosphate or PLP, the active form of vitamin B6, is a highly versatile cofactor that participates in a large number of mechanistically diverse enzymatic reactions in basic metabolism. PLP-dependent enzymes account for ∼1.5% of most prokaryotic genomes and are estimated to be involved in ∼4% of all catalytic reactions, making this an important class of enzymes. Here, we structurally and functionally characterize three novel PLP-dependent enzymes from bacteria in the human microbiome: Two are from Eubacterium rectale, a dominant, nonpathogenic, fecal, Gram-positive bacteria, and the third is from Porphyromonas gingivalis, which plays a major role in human periodontal disease. All adopt the Type I PLP-dependent enzyme fold and structure-guided biochemical analysis enabled functional assignments as tryptophan, aromatic, and probable phosphoserine aminotransferases.

AB - Pyridoxal-5'-phosphate or PLP, the active form of vitamin B6, is a highly versatile cofactor that participates in a large number of mechanistically diverse enzymatic reactions in basic metabolism. PLP-dependent enzymes account for ∼1.5% of most prokaryotic genomes and are estimated to be involved in ∼4% of all catalytic reactions, making this an important class of enzymes. Here, we structurally and functionally characterize three novel PLP-dependent enzymes from bacteria in the human microbiome: Two are from Eubacterium rectale, a dominant, nonpathogenic, fecal, Gram-positive bacteria, and the third is from Porphyromonas gingivalis, which plays a major role in human periodontal disease. All adopt the Type I PLP-dependent enzyme fold and structure-guided biochemical analysis enabled functional assignments as tryptophan, aromatic, and probable phosphoserine aminotransferases.

KW - Biochemical characterization

KW - Crystal structure

KW - Human microbiome

KW - PLP-dependent enzymes

KW - Protein structure initiative

KW - Structural genomics

UR - http://www.scopus.com/inward/record.url?scp=84906847304&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84906847304&partnerID=8YFLogxK

U2 - 10.1002/pro.2493

DO - 10.1002/pro.2493

M3 - Article

C2 - 24888348

AN - SCOPUS:84906847304

VL - 23

SP - 1060

EP - 1076

JO - Protein Science

JF - Protein Science

SN - 0961-8368

IS - 8

ER -