Insights into cephamycin biosynthesis: the crystal structure of CmcI from Streptomyces clavuligerus

Journal of Molecular Biology
Linda M OsterInger Andersson

Abstract

Cephamycin C-producing microorganisms use two enzymes to convert cephalosporins to their 7alpha-methoxy derivatives. Here we report the X-ray structure of one of these enzymes, CmcI, from Streptomyces clavuligerus. The polypeptide chain of the enzyme folds into a C-terminal Rossmann domain and a smaller N-terminal domain, and the molecule packs as a hexamer in the crystal. The Rossmann domain binds S-adenosyl-L-methionine (SAM) and the demethylated product, S-adenosyl-L-homocysteine, in a fashion similar to the common binding mode of this cofactor in SAM-dependent methyltransferases. There is a magnesium-binding site in the vicinity of the SAM site with a bound magnesium ion ligated by residues Asp160, Glu186 and Asp187. The expected cephalosporin binding site near the magnesium ion is occupied by polyethyleneglycol (PEG) from the crystallisation medium. The geometry of the SAM and the magnesium binding sites is similar to that found in cathechol O-methyltransferase. The results suggest CmcI is a methyltransferase, and its most likely function is to catalyse the transfer of a methyl group from SAM to the 7alpha-hydroxy cephalosporin in the second catalytic reaction of cephamycin formation. Based on the docking of the putative s...Continue Reading

References

Jan 1, 1979·Reviews of Infectious Diseases·E O StapleyH B Woodruff
Jul 19, 1974·Nature·M G RossmannK W Olsen
Apr 28, 1968·Journal of Molecular Biology·B W Matthews
Mar 24, 1994·Nature·J VidgrenA Liljas
Feb 7, 1998·Structure·G J Kleywegt, R J Read
Sep 17, 1999·Bioinformatics·T A TatusovaJ A Ostell
Oct 24, 2003·Acta Crystallographica. Section D, Biological Crystallography·R W Grosse-Kunstleve, P D Adams
Jan 14, 2004·Nature Structural & Molecular Biology·Karin ValegårdInger Andersson
Jul 24, 2004·Acta Crystallographica. Section D, Biological Crystallography·Alexander W Schüttelkopf, Daan M F van Aalten
Jan 1, 1996·Acta Crystallographica. Section D, Biological Crystallography·J P Abrahams, A G Leslie
Jul 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·A PerrakisV S Lamzin
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Sep 29, 2004·Current Opinion in Chemical Biology·Gunhild LayerWolf-Dieter Schubert

❮ Previous
Next ❯

Citations

May 27, 2008·The Journal of Biological Chemistry·Shanteri SinghJon S Thorson
Nov 11, 2008·PloS One·Patricia RenestoDidier Raoult
Mar 29, 2008·Protein Science : a Publication of the Protein Society·Clare J McClevertyScott A Lesley
Jan 25, 2011·Microbial Biotechnology·Juan F MartínCarlos García-Estrada
Aug 19, 2008·Journal of Molecular Biology·Jang-Hee ChoSangkee Rhee
May 29, 2018·Natural Product Reports·Patrick RabeChristopher T Lohans
Nov 9, 2012·Natural Product Reports·Refaat B HamedChristopher J Schofield
Jan 13, 2015·Journal of Microbiology & Biology Education·Pamela A Marshall
Oct 4, 2021·Journal of Industrial Microbiology & Biotechnology·Paloma Liras, Juan F Martín

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.