Navigation Links
Scripps scientists find structure of a protein that makes cancer cells resistant to chemotherapy
Date:3/26/2009

r as well as Scripps Research, determined the structure of P-gp using a technique in structural biology known as x-ray crystallography, which involves making crystals of ordered arrays of protein and then blasting the frozen crystals with x-ray radiation. The atoms in the protein crystals cause the x-rays to diffract, and the scientists collect and analyze the pattern of diffraction to solve the atomic-level structure of the proteins.

"The biggest challenge was to get enough protein to purify and make crystals from it," says Stephen Aller, Ph.D., a postdoctoral fellow in Chang's laboratory and first author of the new study.

Once the scientists succeeded in performing the x-ray crystallography and solving the structure, they found that the mouse protein P-gp, which is 87 percent identical to its human counterpart, has the shape of an upside down "v" or a tipi with a large cavity inside. The cavity's interior is lined with amino acids that bind to various substances, holding them in place. The top part of the tipi resides inside the cell membrane and has two openings for substances to enter; the bottom portion sticks out inside the cell, ending in two dumbbell-shaped arms.

This overall shape is strikingly similar to that of another protein, MsbA, that transports lipids out of bacteria. This similarity suggests that P-gp works by bringing the two dumbbell-shaped arms together on the inside of the cell and opening the closed end toward the outside of the cell, essentially reversing direction of the "v" or tipi so any substance caught inside the protein's cavity is ejected from the cell.

While the new study shows another similarity between MsbA and P-gpboth binding cavities are lined with hydrophobic amino acidsit turns out that the mammalian P-gp has many more such amino acids and a greater variety of them, including aromatic amino acids that are known to bind many different substances (substances acted on by enzymes).

"Un
'/>"/>

Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

Page: 1 2 3

Related biology news :

1. Scripps research scientists watch as individual alpha-synuclein proteins change shape
2. Scripps research team identifies key molecules that inhibit viral production
3. Historical photographs expose decline in Floridas reef fish, new Scripps study finds
4. Scripps scientists create first crystal structure of an intermediate particle in virus assembly
5. Scripps scientists develop first examples of RNA that replicates itself indefinitely
6. Scripps Research scientists shed light on how DNA is unwound so that its code can be read
7. Dolphin population stunted by fishing activities, Scripps/NOAA study finds
8. Scripps research team defines new painkilling chemical pathway
9. Scripps research scientists identify blood component that turns bacteria virulent
10. Scripps research scientists identify compounds for stem-cell production from adult cells
11. Scripps Florida scientists awarded $1.5M to fight major water and food parasites
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:7/30/2015)... 30, 2015 Cellecta, Inc., a U.S.-based ... analysis and biomarker discovery, announced the release of ... targeting all human protein coding genes. CRISPR technology ... a gene,s function. Cellecta,s new Human Whole Genome ... tool so that researchers can investigate in a ...
(Date:7/21/2015)... Today, ZTE announced its Android smartphone Axon, ... expected revenues in 2015 that relate to sales of FPC1025 for ... approximately 2,200 MSEK for 2015. Jörgen Lantto, CEO of ... in China and we are proud that ... for Axon , its first ...
(Date:7/13/2015)... Conn. , Jul. 13, 2015 NXT-ID, ... "Company"), a biometric authentication company focused on the ... has filed provisional patent 62/188684 for ... achieves another new convenient and secure method to ... new, innovative payment methods, introduced with its groundbreaking ...
Breaking Biology News(10 mins):CELLECTA, INC. Announces Launch of Human Whole Genome CRISPR Knockout Library 2FPC's Touch Fingerprint Sensor FPC1025 in ZTE's Smartphone Axon 2NXT-ID Patents Behavior-Directed Payments 2NXT-ID Patents Behavior-Directed Payments 3NXT-ID Patents Behavior-Directed Payments 4
... Biologically Inspired Engineering at Harvard University have developed ... toughness, and versatility of one of nature,s more ... the new material, called "Shrilk," could one day ... safely in a variety of medical applications. ...
... is available in German . Plants ... through photosynthesis in the leaves. However, they do not have ... this vital fuel. Instead, they use pump proteins in their ... Carnegie Institution for Science in California, Alisdair Fernie from the ...
... a native frog rising in the West. With a ... Davidson has young children imagining the life cycles and life ... cheering for the underfrog. "Cheery: The true adventures of ... Davidson and brought to life by graphic artist Michael Hagelberg. ...
Cached Biology News:Inspired by insect cuticle, Wyss Institute develops material that's tough and strong 2Sugar pump in plants identified 2Sugar pump in plants identified 3Picture book portrays a 'hoppy' future for endangered frogs 2Picture book portrays a 'hoppy' future for endangered frogs 3
(Date:7/30/2015)... , July 30, 2015 Ascendis ... company that applies its innovative TransCon technology to ... top-line results from a six-month Phase 2 study ... TransCon Growth Hormone in 53 treatment-naïve, pre-pubertal children ... "We are extremely pleased with the top-line results ...
(Date:7/30/2015)... ... July 30, 2015 , ... GEA's Pony™ NS2006L ... operation up to 1500 bar. The sanitary design gauge of the NS2006L is ... , The Pony™ NS2006L homogenizer is an ideal solution for the processing of ...
(Date:7/29/2015)... US-Australian drug discovery company, Novogen Limited (ASX: ... committed to progressing its ground-breaking technology platforms to Phase ... ensure the Company delivers the best value for shareholders. ... , said the Company currently had an extensive program ... programs and academic partnerships and initiatives, and he was ...
(Date:7/29/2015)... FRANCISCO , July 29, 2015  AsureQuality ... mobile molecular testing for applications in food and ... hand-held, battery powered real-time PCR device, the Freedom4. ... farm right through to the supermarket shelf for ... This includes involvement in animal disease control and ...
Breaking Biology Technology:Ascendis Pharma A/S Announces Positive Top-line Results from a Phase 2 Pediatric Study of Once-Weekly TransCon Growth Hormone for the Treatment of Growth Hormone Deficiency 2Ascendis Pharma A/S Announces Positive Top-line Results from a Phase 2 Pediatric Study of Once-Weekly TransCon Growth Hormone for the Treatment of Growth Hormone Deficiency 3Ascendis Pharma A/S Announces Positive Top-line Results from a Phase 2 Pediatric Study of Once-Weekly TransCon Growth Hormone for the Treatment of Growth Hormone Deficiency 4Ascendis Pharma A/S Announces Positive Top-line Results from a Phase 2 Pediatric Study of Once-Weekly TransCon Growth Hormone for the Treatment of Growth Hormone Deficiency 5Ascendis Pharma A/S Announces Positive Top-line Results from a Phase 2 Pediatric Study of Once-Weekly TransCon Growth Hormone for the Treatment of Growth Hormone Deficiency 6Ascendis Pharma A/S Announces Positive Top-line Results from a Phase 2 Pediatric Study of Once-Weekly TransCon Growth Hormone for the Treatment of Growth Hormone Deficiency 7GEA Announces the Pony™ NS2006L… a Self-contained, High Pressure Lab Homogenizer for Product Development Ensuring Maximum Efficiency and Safety 2Newly Appointed Acting CEO Outlines Immediate Plans for Novogen 2Newly Appointed Acting CEO Outlines Immediate Plans for Novogen 3Newly Appointed Acting CEO Outlines Immediate Plans for Novogen 4Newly Appointed Acting CEO Outlines Immediate Plans for Novogen 5Newly Appointed Acting CEO Outlines Immediate Plans for Novogen 6Newly Appointed Acting CEO Outlines Immediate Plans for Novogen 7Newly Appointed Acting CEO Outlines Immediate Plans for Novogen 8Newly Appointed Acting CEO Outlines Immediate Plans for Novogen 9Newly Appointed Acting CEO Outlines Immediate Plans for Novogen 10AsureQuality and Ubiquitome Partner on Applications for Mobile Molecular Food Safety Testing 2
... to File Appeal, BERKELEY HEIGHTS, N.J., Jan. ... today that the Company has received,notice from the ... based upon the Company,s non-compliance with the stockholders, ... the Company,s,common stock is subject to delisting from ...
... YORK, Jan. 11 "I am pleased to announce ... Ltd. and Kemfast,Ltd (collectively Kemfast) and its MC Technologies ... L.P. to form Haas TCM Group Inc.,ICMS Holdings, Inc. ... be integrated with Haas TCM Group Inc. The focus ...
... ... the Term ,Bio-identical, SPOKANE, Wash., Jan. 11 "The ... --,progesterone, and other compounded hormones was very surprising to me ... Cheryle,Hart, M.D. She is Mayo Clinic trained and Board certified ...
Cached Biology Technology:Genta Receives Notice of Non-Compliance With NASDAQ Rule 2Genta Receives Notice of Non-Compliance With NASDAQ Rule 3The Jordan Company, L.P. Has Teamed with the Management of Haas TCM Inc. to Form Haas TCM Group Inc. 2The Jordan Company, L.P. Has Teamed with the Management of Haas TCM Inc. to Form Haas TCM Group Inc. 3Bio-Identical Hormone Menopause Doctor Responds to Outrageous FDA News 2
... Custom peptide microarrays designed for quantitative ... samples and built on the flexible ... Thousands of customer specified sequences can ... can provide assistance with custom sequence ...
... for OPA1-01009, OPEP-01009 is a 16 amino acid (amino acids ... factor (DFF). The sequence of this peptide is (amino ... - S - V - K - L - R ... - R - K(18). This peptide may be ...
... Arrays are intended for laboratory research use ... in neutral buffered formalin and embedded in ... performed by certified pathologists. Tissue cores ... relocated into a new recipient paraffin block, ...
... Processing of Microarrays Using the New FAST(tm) ... slide plate is designed to hold four, ... incubation chambers in a microplate footprint for ... dimensions meet the standards recommended by the ...
Biology Products: