Homology modelling of the enzyme P450 17α-hydroxylase/ 17,20-lyase - a target for prostate cancer chemotherapy - from the crystal structure of P450BM-3

David F. Burke; Charles A. Laughton; Stephen Neidle

Homology modelling of the enzyme P450 17α-hydroxylase/ 17,20-lyase - a target for prostate cancer chemotherapy - from the crystal structure of P450BM-3

David F. Burke, Charles A. Laughton^*, Stephen Neidle

^*Corresponding author for this work

Centre for Host Microbiome Interactions

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

Abstract

Using homology modelling techniques the structure of cytochrome P450 17α-hydroxylase/17-20 lyase (P450c17) has been predicted from the crystal structure of P450BM-3. The resulting structure has been compared to a previous model, built on the basis of homology to P450cam. Despite considerable structural differences between the two template structures, the two derived models for P450c17 show a high degree of similarity in the active-site region. As before, a bilobal active-site cavity is predicted, and we hypothesize that binding of the steroid in one lobe of the active site is associated with the hydroxylase activity of the enzyme, whilst binding in the other is associated with the lyase reaction.

Original language	English
Pages (from-to)	113-123
Number of pages	11
Journal	Anti-Cancer Drug Design
Volume	12
Issue number	2
Publication status	Published - Mar 1997

Keywords

Chemotherapy
Homology modelling
P450BM-3
P450c17
Prostate cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Cite this

@article{a7e0dd53d1d34e8d895a39a8103390e4,

title = "Homology modelling of the enzyme P450 17α-hydroxylase/ 17,20-lyase - a target for prostate cancer chemotherapy - from the crystal structure of P450BM-3",

abstract = "Using homology modelling techniques the structure of cytochrome P450 17α-hydroxylase/17-20 lyase (P450c17) has been predicted from the crystal structure of P450BM-3. The resulting structure has been compared to a previous model, built on the basis of homology to P450cam. Despite considerable structural differences between the two template structures, the two derived models for P450c17 show a high degree of similarity in the active-site region. As before, a bilobal active-site cavity is predicted, and we hypothesize that binding of the steroid in one lobe of the active site is associated with the hydroxylase activity of the enzyme, whilst binding in the other is associated with the lyase reaction.",

keywords = "Chemotherapy, Homology modelling, P450BM-3, P450c17, Prostate cancer",

author = "Burke, {David F.} and Laughton, {Charles A.} and Stephen Neidle",

year = "1997",

month = mar,

language = "English",

volume = "12",

pages = "113--123",

journal = "Anti-Cancer Drug Design",

issn = "0266-9536",

publisher = "Cognizant Communication Corporation",

number = "2",

}

TY - JOUR

T1 - Homology modelling of the enzyme P450 17α-hydroxylase/ 17,20-lyase - a target for prostate cancer chemotherapy - from the crystal structure of P450BM-3

AU - Burke, David F.

AU - Laughton, Charles A.

AU - Neidle, Stephen

PY - 1997/3

Y1 - 1997/3

N2 - Using homology modelling techniques the structure of cytochrome P450 17α-hydroxylase/17-20 lyase (P450c17) has been predicted from the crystal structure of P450BM-3. The resulting structure has been compared to a previous model, built on the basis of homology to P450cam. Despite considerable structural differences between the two template structures, the two derived models for P450c17 show a high degree of similarity in the active-site region. As before, a bilobal active-site cavity is predicted, and we hypothesize that binding of the steroid in one lobe of the active site is associated with the hydroxylase activity of the enzyme, whilst binding in the other is associated with the lyase reaction.

AB - Using homology modelling techniques the structure of cytochrome P450 17α-hydroxylase/17-20 lyase (P450c17) has been predicted from the crystal structure of P450BM-3. The resulting structure has been compared to a previous model, built on the basis of homology to P450cam. Despite considerable structural differences between the two template structures, the two derived models for P450c17 show a high degree of similarity in the active-site region. As before, a bilobal active-site cavity is predicted, and we hypothesize that binding of the steroid in one lobe of the active site is associated with the hydroxylase activity of the enzyme, whilst binding in the other is associated with the lyase reaction.

KW - Chemotherapy

KW - Homology modelling

KW - P450BM-3

KW - P450c17

KW - Prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=0030945393&partnerID=8YFLogxK

M3 - Article

C2 - 9113066

AN - SCOPUS:0030945393

SN - 0266-9536

VL - 12

SP - 113

EP - 123

JO - Anti-Cancer Drug Design

JF - Anti-Cancer Drug Design

IS - 2

ER -

Homology modelling of the enzyme P450 17α-hydroxylase/ 17,20-lyase - a target for prostate cancer chemotherapy - from the crystal structure of P450BM-3

Abstract

Keywords

UN SDGs

Other files and links

Fingerprint

Cite this