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Seeing is believing: the impact of structural genomics on antimicrobial drug discovery

Nature Reviews Microbiology volume 2, pages 739–746 (2004)Cite this article

Abstract

Over the past decade, the availability of complete microbial genome sequences has led to changes in the strategies that are used to search for novel anti-infectives. However, despite the identification of many new potential drug targets, novel antimicrobial agents have been slow to emerge from these efforts. In part, this reflects the long discovery and development times that are needed to bring new drugs to market and the bottlenecks at the stages of identifying good lead compounds and optimizing these leads into drug candidates. Structural genomics will hopefully provide opportunities to overcome these bottlenecks and populate the antimicrobial pipeline.

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Figure 1: From clone to high-resolution protein structure.
Figure 2: Structure-guided antimicrobial drug discovery.
Figure 3: Protein–ligand co-structures.

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Acknowledgements

The author thanks former colleagues at Affinium Pharmaceuticals for the opportunity to participate in building a structural genomics pipeline and to understand the value that structural biology can bring to drug discovery when it can keep pace with the medicinal chemistry cycle. In addition, J. Berman, D. Biek, A. Dharamsi, N. Kaplan and R. Lam provided excellent comments on drafts of the manuscript.

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  1. MBS Associates, 38 Avenue Road, Suite 601, Toronto, M5R 2G2, Ontario, Canada

    Molly B. Schmid

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  1. Molly B. Schmid
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I am a former employee of Affinium Pharmaceuticals, a structure-guided drug discovery company.

Related links

Related links

DATABASES

Entrez

Escherichia coli

Haemophilus influenzae

Lon

Mycobacterium tuberculosis

OmpT

Staphylococcus aureus

Streptococcus pneumoniae

Protein Data Bank

DNA gyrase

FabH–acetyl-coA complex

LpxC

penicillin-binding protein

30S ribosomal subunit

50S ribosomal subunit

RNA polymerase

FURTHER INFORMATION

Completed microbial genomes

PEC database

PEDANT database

TargetDB database

The Institute for Genomic Research (TIGR)

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Schmid, M. Seeing is believing: the impact of structural genomics on antimicrobial drug discovery. Nat Rev Microbiol 2, 739–746 (2004). https://doi.org/10.1038/nrmicro978

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