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Highlights on Trypanosomatid Aminoacyl-tRNA Synthesis

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Book cover Proteins and Proteomics of Leishmania and Trypanosoma

Part of the book series: Subcellular Biochemistry ((SCBI,volume 74))

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Abstract

Aminoacyl-tRNA synthetases aaRSs are responsible for the aminoacylation of tRNAs in the first step of protein synthesis. They comprise a group of enzymes that catalyze the formation of each possible aminoacyl-tRNA necessary for messenger RNA decoding in a cell. These enzymes have been divided into two classes according to structural features of their active sites and, although each class shares a common active site core, they present an assorted array of appended domains that makes them sufficiently diverse among the different living organisms. Here we will explore what is known about the diversity encountered among trypanosomatids’ aaRSs that has helped us not only to understand better the biology of these parasites but can be used rationally for the design of drugs against these protozoa.

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Abbreviations

A:

Adenine

aa-AMP:

aaRS, 4, 5 aminoacyl-adenylate complexed with aminoacyl-tRNA synthetase

aaRS:

Aminoacyl-tRNA synthetase

aa-tRNA:

Aminoacyl-tRNA

AC1:

Anticodon binding motif

AC2:

Anticodon binding motif

AIDQ:

TrpRS and TyrRS motif present in the catalytic site (alanine, isoleucine, aspartate, glutamine)

AlaRS:

Alanyl-tRNA synthetase

AMP:

Adenosine-5′-monophosphate

Arg:

Arginine

ArgRS:

Arginyl-tRNA synthetase

Asn:

Asparagine

AsnRS:

Asparaginyl-tRNA synthetase

Asp:

Aspartate

AspRS:

Aspartyl-tRNA synthetase

ATP:

Adenosine-5′-triphosphate

AUA:

Isoleucine codon

AUG:

Methionine codon

C:

Cytosine

CPK:

Coloring convention designed by Robert Corey and Linus Pauling, and improved by Walter Koltun.

Cys:

Cysteine

CysRS:

Cysteinyl-tRNA synthetase

E:

Glutamate

E. coli:

Escherichia coli

eEFSec:

Selenocysteine elongation factor

EMAP II-like domain:

Endothelial monocyte-activating polypeptide II-like domain

ESE:

Eukaryotic specific extension present in Tryptophanyl-tRNA synthetases

fmet:

Formylmethionine

FTHF:

N10-formyltetrahydrofolate

G:

Guanine

GatCAB:

tRNA dependent amidotransferase of Archaea, bacteria and eukaryotic organelles

GatDE:

Archaeal specific tRNA dependent amidotransferase

GatFAB:

Yeast specific tRNA dependent amidotransferase

GLDQ:

Trypanosomatid TyrRS motif present in the catalytic site (glycine, leucine, aspartate, glutamine)

Gln:

Glutamine

GlnRS:

Glutaminyl-tRNA synthetase

Glu:

Glutamate

GluRS:

Glutamyl-tRNA synthetase

Gly:

Glycine

GlyRS:

Glycyl-tRNA synthetase

GTP:

Guanosine-5′-triphosphate

GXDQ:

TrpRS motif present in bacteria (glycine, any amino acid, aspartate, glutamine)

H:

Histidine

HAM:

Histidyl-adenosinemonophosphate

HARS1:

Human histidyl-tRNA synthetase 1

HARS2:

Human histidyl-tRNA synthetase 2

HIAQ:

Motif present in the active site of the trypanosomal tyrosyl-tRNA synthetase in place of motif

HIGH:

(Histidine, isoleucine, alanine, glutamine)

HIGH:

Motif presents in the active site of aaRS class I (histidine, isoleucine, glycine, histidine)

His:

Histidine

HisRS:

Histidyl-tRNA synthetase

Ile:

Isoleucyl

IleRS:

Isoleucyl-tRNA synthetase

Kcat :

Catalytic constant

Ki :

Dissociation constant for inhibitor binding

KISKS:

Motif present in the active site of trypanosomatid methyl-tRNA synthetase (lysine, isoleucine, serine, lysine, serine)

Km :

Michaelis Menten constant

KMSKS:

Motif present in the active site of aminoacyl-tRNA synthetases class I (lysine, methionine, serine, lysine, serine)

L30:

Ribosomal protein

Leu:

Leucine

LeuRS:

Leucyl-tRNA synthetase

Lys:

Lysine

LysRS:

Lysyl-tRNA synthetase

MAMP:

Methionyl adenylate

Met:

Methionine

MetRS:

Methionyl-tRNA synthetase

Mg+2 :

Magnesium ion

mRNA:

Messenger ribonucleic acid

MTF:

Methionyl-tRNA formyltransferase

PDB:

Protein data bank

Phe:

Phenylalanine

PheRS:

Phenylalanyl-tRNA synthetase

PLP:

Pyridoxal phosphate

PPi :

Pyrophosphate

Pro:

Proline

ProRS:

Prolyl-tRNA synthetase

PSTK:

O-phosphoseryl-tRNA kinase

Pyl:

Pyrrolysine

PylRS:

Pyrrolysyl-tRNA synthetase

SBP2:

SECIS binding protein

SCF:

Stem contact fold

Sec:

Selenocysteine

SECIS:

22, 23, 26, 27, 31, 40

Sel1:

Kinetoplastid specific selenoprotein

selA:

Selenocysteine synthase (bacterial)

SelK:

Selenoprotein K

SelT:

Selenoprotein T

SelTryp:

Kinetoplastid specific selenoprotein

Sep:

Phosphoserine

SepRS:

Phosphoseryl-tRNA synthetase

SepSecS:

O-phospho-L-seryl-tRNASec: L-selenocysteinyl-tRNA synthase

Ser:

Serine

SerRS:

Seryl-tRNA synthetase

SPS2:

Selenophosphate synthase

ThrRS:

Threonyl-tRNA synthetase

Tpr:

Tryptophan

tRNA:

Transfer ribonucleic acid

tRNAfMet :

Formylmethionine tRNA isoacceptor

tRNAMet-e :

Methionine elongator tRNA isoacceptor

tRNAmet-i :

Methionine initiator tRNA isoacceptor

TrpRS:

Tryptophanyl-tRNA synthetase

Tyr:

Tyrosine

TyrRS:

Tyrosine tRNA-synthetase

U:

Uracyl

UAA:

Termination codon (uracyl, adenine, adenine)

UAG:

Termination codon (uracyl, adenine, guanine)

UGA:

Termination codon (uracyl, guanine, adenine)

V:

Valine

Val:

Valine

ValRS:

Valy-tRNA synthetase

W:

Tryptophan

WHEP:

Helix-turn-helix domain found in some aminoacyl-tRNA synthetasese

Ψ:

Pseudouridine

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Acknowledgments

 This work was supported by grants from FAPERJ, CNPq and WHO-TDR. I thank Dr. André Santos for inviting me to write this chapter and me deeply grateful to Dr. Shipra Srihari for editing the English. I also would like to express my gratitude to the invaluable contribution of the reviewers.

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Authors and Affiliations

  1. Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Carla Polycarpo

  2. Cidade Universitária Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular, Avenida Carlos Chagas Filho, 373, Centro de Ciências da Saúde, Bloco D, subsolo, sala 5, Rio de Janeiro, RJ, 21941-902, Brazil

    Carla Polycarpo

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  1. Carla Polycarpo
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Correspondence to Carla Polycarpo .

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Editors and Affiliations

  1. Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil

    André L.S. Santos

  2. Departamento de Microbiologia Geral, Ins. de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil

    Marta H. Branquinha

  3. Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil

    Claudia M. d’Avila-Levy

  4. Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil

    Lucimar F. Kneipp

  5. Departamento de Biologia Celular e Molecular, Instituto de Biologia Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil

    Cátia L. Sodré

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Polycarpo, C. (2014). Highlights on Trypanosomatid Aminoacyl-tRNA Synthesis. In: Santos, A., Branquinha, M., d’Avila-Levy, C., Kneipp, L., Sodré, C. (eds) Proteins and Proteomics of Leishmania and Trypanosoma. Subcellular Biochemistry, vol 74. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7305-9_12

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