Vallone Lab
  • Home
  • Research
  • People
  • News
    • Science
    • Events
  • Contact
  • Menu Menu

P450 Cytochromes and antibiotic biosynthesis

OleP‐6DEB complex. A) Superposition of the open (green) and closed (wheat) conformations of OleP‐6DEB complex

The P450 OleP bound to the inhibitor clotrimazole

A designed mutation of the P450 EryK allowed activity on the shunt product ErB

We study the structure of microbial P450 cytochromes to decipher substrate recognition detrminants and the structural transitions involved in the antibiotic tailoring steps, crucial for obtaining the final active compound or to engineer the production of new ones.

We demonstrated the structural selection mechanism involved in the activity of the EryK P450, leading to Erythromycin A production and we engineered a variant of the enzyme that could eliminate the presence of the shunt product Erythromycin B.

We are currently analysing the substrate specificity and enzyme dynamics of the OleP P450, endowed with substrate promiscuity and carrying out a rare and potentially very interesting epoxidation within the antibiotic oleandomycin.

Main Publications

Substrate-induced conformational change in cytochrome P450 OleP.
Parisi G, Montemiglio LC, Giuffrè A, Macone A, Scaglione A, Cerutti G, Exertier C, Savino C, Vallone B.
FASEB J. 2019 Feb;33(2):1787-1800. doi: 10.1096/fj.201800450RR. Epub 2018 Sep 12.
PMID: 30207799

Functional analysis and crystallographic structure of clotrimazole bound OleP, a cytochrome P450 epoxidase from Streptomyces antibioticus involved in oleandomycin biosynthesis.
Montemiglio LC, Parisi G, Scaglione A, Sciara G, Savino C, Vallone B.
Biochim Biophys Acta. 2016 Mar;1860(3):465-75. doi: 10.1016/j.bbagen.2015.10.009. Epub 2015 Oct 22.
PMID: 26475642

Redirecting P450 EryK specificity by rational site-directed mutagenesis.
Montemiglio LC, Macone A, Ardiccioni C, Avella G, Vallone B, Savino C.
Biochemistry. 2013 May 28;52(21):3678-87. doi: 10.1021/bi400223j. Epub 2013 May 16.
PMID: 23597312

Azole drugs trap cytochrome P450 EryK in alternative conformational states.
Montemiglio LC, Gianni S, Vallone B, Savino C.
Biochemistry. 2010 Nov 2;49(43):9199-206. doi: 10.1021/bi101062v.
PMID: 20845962

Investigating the structural plasticity of a cytochrome P450: three-dimensional structures of P450 EryK and binding to its physiological substrate.
Savino C, Montemiglio LC, Sciara G, Miele AE, Kendrew SG, Jemth P, Gianni S, Vallone B.
J Biol Chem. 2009 Oct 16;284(42):29170-9. doi: 10.1074/jbc.M109.003590. Epub 2009 Jul 22.
PMID: 19625248
Free PMC Article

Cloning, expression, purification, crystallization and preliminary X-ray crystallographic analysis of C-12 hydroxylase EryK from Saccharopolyspora erythraea.
Savino C, Sciara G, Miele AE, Kendrew SG, Vallone B.
Protein Pept Lett. 2008;15(10):1138-41.
PMID: 19075827

  • Share on Facebook
  • Share on Twitter
  • Share on Whatsapp
  • Share on LinkedIn
  • Share by Mail
  • Share on Telegram
All/Grants/Research Lines
Ferritin - Transferrin Receptor
April 1, 2020

Ferritin / Transferrin Receptor

OleP‐6DEB complex. A) Superposition of the open (green) and closed (wheat) conformations of OleP‐6DEB complex
April 1, 2020

P450

Cavities in NgbCO (blue) and unligated metNgb (yellow) as determined by using surfnet (46). The position of Ser-55 is highlighted in green.
April 1, 2020

Globins

Fluorescence of human SRD5As and TECR
March 28, 2020

Membrane Proteins and Drug Design

March 28, 2020

Kinases and Targeted Therapy

March 28, 2020

Fungal enzymes and cellulose degradation

March 27, 2020

PROMETEUS-RISE Protein and Membrane Technology Consortium

March 27, 2020

X-PROBE Innovative Training Network

March 27, 2020

PROMETEUS-RISE Protein and Membrane Technology Consortium

March 27, 2020

X-PROBE Innovative Training Network

Ferritin - Transferrin Receptor
April 1, 2020

Ferritin / Transferrin Receptor

OleP‐6DEB complex. A) Superposition of the open (green) and closed (wheat) conformations of OleP‐6DEB complex
April 1, 2020

P450

Cavities in NgbCO (blue) and unligated metNgb (yellow) as determined by using surfnet (46). The position of Ser-55 is highlighted in green.
April 1, 2020

Globins

Fluorescence of human SRD5As and TECR
March 28, 2020

Membrane Proteins and Drug Design

March 28, 2020

Kinases and Targeted Therapy

March 28, 2020

Fungal enzymes and cellulose degradation

 
 

© Copyright – Beatrice Vallone – Webdesign Fabio Baldanello – Cookies Policy – Privacy Policy

© Copyright – Beatrice Vallone
Webdesign Fabio Baldanello
Cookies Policy – Privacy Policy

Ferritin / Transferrin Receptor Ferritin - Transferrin Receptor Cavities in NgbCO (blue) and unligated metNgb (yellow) as determined by using surfnet (46). The position of Ser-55 is highlighted in green. Globins
Scroll to top

This site uses cookies. By continuing to browse the site, you are agreeing to our use of cookies.

Accept settingsSettings

Cookie and Privacy Settings



How we use cookies

We may request cookies to be set on your device. We use cookies to let us know when you visit our websites, how you interact with us, to enrich your user experience, and to customize your relationship with our website.

Click on the different category headings to find out more. You can also change some of your preferences. Note that blocking some types of cookies may impact your experience on our websites and the services we are able to offer.

Essential Website Cookies

These cookies are strictly necessary to provide you with services available through our website and to use some of its features.

Because these cookies are strictly necessary to deliver the website, refuseing them will have impact how our site functions. You always can block or delete cookies by changing your browser settings and force blocking all cookies on this website. But this will always prompt you to accept/refuse cookies when revisiting our site.

We fully respect if you want to refuse cookies but to avoid asking you again and again kindly allow us to store a cookie for that. You are free to opt out any time or opt in for other cookies to get a better experience. If you refuse cookies we will remove all set cookies in our domain.

We provide you with a list of stored cookies on your computer in our domain so you can check what we stored. Due to security reasons we are not able to show or modify cookies from other domains. You can check these in your browser security settings.

Google Analytics Cookies

These cookies collect information that is used either in aggregate form to help us understand how our website is being used or how effective our marketing campaigns are, or to help us customize our website and application for you in order to enhance your experience.

If you do not want that we track your visit to our site you can disable tracking in your browser here:

Other external services

We also use different external services like Google Webfonts, Google Maps, and external Video providers. Since these providers may collect personal data like your IP address we allow you to block them here. Please be aware that this might heavily reduce the functionality and appearance of our site. Changes will take effect once you reload the page.

Google Webfont Settings:

Google Map Settings:

Google reCaptcha Settings:

Vimeo and Youtube video embeds:

Other cookies

The following cookies are also needed - You can choose if you want to allow them:

Privacy Policy

You can read about our cookies and privacy settings in detail on our Privacy Policy Page.

Privacy Policy
Accept settingsHide notification only