Projects - Respiratory Disease

Protein

Description

Statistics

TNF-a

 

The name Tumor necrosis factor-a (TNF-a) originates from its ability to kill tumor cells. It is a cytokine that induces protective inflammatory reactions but also causes severe damage when produced in excess, as in rheumatoid arthritis and septic shock. Our interest is in respiratory disease where it is also a recognised potential drug target.

In test jobs, this query gave more hits than usual in typical times.



 
query: 1BKC-Q1
% jobs complete: 100.000
molecules: 39,627,605
hits: 404,514
time: 8:001:01:40:17
Pictures   K Maskos et al Proc Natl Acad Sci (1998) 95.7 p3408-12   last updated: 18:11 on 02-AUG-05

Expoxide Hydrolase

 

It has been suggested that Expoxide Hydrolase might alleviate inflammation in the lungs.

We expect this query to give typical numbers of hits with shorter than average job times.



 
query: 1CR6-Q1
% jobs complete: 100.000
molecules: 39,627,612
hits: 26,715
time: 1:137:17:24:26
Pictures   M A Argiriadi et al Proc Nat Acad Sci (1999) 96 p10637   last updated: 12:11 on 06-JUN-05

Phosphodiesterase 4 (PDE4)

 

Phosphodiesterase 4 (PDE4) is a recognised anti-inflammatory drug target. However, it has been suggested that existing inhibitors lack the specificity or have problematic side-effects.

The time taken for jobs for this query is typical giving few hits.



 
query: 1F0J-Q1
% jobs complete: 100.000
molecules: 39,627,586
hits: 12,222
time: 3:243:06:29:13
Pictures   R X Xu et al, Science (2000) 288 p1822   last updated: 00:12 on 23-JUN-05

Interleukin-1 receptor type 1

 

Blocking Interleukin-1 receptor type 1 has the potential to reduce the effect of elevated Interleukin-1 levels which is associated with inflammation in the lungs and other tissues.

We expect this query to give average numbers of hits with longer than typical job times.



 
query: 1G0Y-Q1
% jobs complete: 100.000
molecules: 39,627,269
hits: 315,688
time: 25:146:18:18:00
Pictures   G P A Vigers at al Structure (2000) 275 p36927   last updated: 12:22 on 07-AUG-05

Thymidylate kinase (TMPK)

 

This kinase converts thymidine monophosphate (TMP) to the di- and tri-phosphates. Inhibiting this process would be expected to significantly disrupt the cell cycle (ie growth). There is sufficient variation from the mammalian form and that found in mycobacterium tuberculosis to give scope for selective inhibition.

This query gave relatively few hits from a selection of test jobs.



 
query: 1G3U-Q1
% jobs complete: 100.000
molecules: 39,865,317
hits: 84,945
time: 5:184:12:28:01
Pictures   I Li de la Sierra et al J Mol Biol (2001) 311 p87-100   last updated: 06:16 on 08-NOV-04

UDP-Galactopyranose mutase

 

UDP-Galactopyranose mutase is an essential enzyme for mycobacteria including tuberculosis. It makes Uridine diphosphogalactofuranose (UDP-Galf) which is converted to the d-galactofuranose (Galf) found in cell walls. Fortunately the enzyme is not found in humans reducing the scope for site-effects.

We expect this queries to give above average numbers of hits with longer than typical job times.



 
query: 1I8T-Q1
% jobs complete: 100.000
molecules: 39,627,472
hits: 482,738
time: 12:027:02:15:28
Pictures   D A Sanders et al Nat Struct Biol (2001) 8.10 p858-63   last updated: 06:06 on 08-APR-05

MRP14

 

MRP14 is a Ca(2+)-binding protein from the S100 family of proteins thought to play a role during inflammation of membranes.

We expect this query to give above average numbers of hits with longer job times than typical.



 
query: 1IRJ-Q2
% jobs complete: 100.000
molecules: 39,645,672
hits: 69,611
time: 19:157:03:44:42
Pictures   H Itou et al, J Mol Biol (2002) 316.2 p265-76.   last updated: 00:05 on 20-SEP-05

Macrophage Elastase Mmp-12

 

Macrophage Elastase Mmp-12 is a member of the family of matrix metalloproteinases (MMPs) that play an important role in inflammatory processes contributing to tissues changes and destruction. In the lung, elastin is destroyed and it has been suggested that Mmp-12 activity causes emphysema.

The jobs for this query are typical (ie around 12 hours on a 1GHz PC).



 
query: 1JIZ-Q1
% jobs complete: 100.000
molecules: 39,627,431
hits: 527,085
time: 11:352:09:56:03
Pictures   H Nar et al J Mol Biol (2001) 312 p743   last updated: 18:13 on 30-MAR-05

Histamine methyl transferase

 

The hormone histamine plays a key role in bronchial asthma as well as gastric acid secretion. Histamine interacts with histamine methyltransferase. Molecules which block this interact have capability to be new anti-histamine drugs for asthma treatment.

We expect this queries to give few hits with typical job times.



 
query: 1JQD-Q2
% jobs complete: 100.000
molecules: 39,627,323
hits: 5,304
time: 6:058:06:39:38
Pictures   J R Horton et al Structure (2001) 9.9 p837-49   last updated: 06:04 on 10-APR-05

Histamine methyl transferase

 

The hormone histamine plays a key role in bronchial asthma as well as gastric acid secretion. Histamine interacts with histamine methyltransferase. Molecules which block this interact have capability to be new anti-histamine drugs for asthma treatment. This query is based on a different crystal structure than 1jqd-q2.

We expect this queries to give normal numbers of hits with in typical times.



 
query: 1JQE-Q1
% jobs complete: 100.000
molecules: 39,627,882
hits: 167,815
time: 18:013:12:02:03
Pictures   J R Horton et al Structure (2001) 9.9 p837-49   last updated: 18:28 on 07-AUG-05

Interleukin-10 receptor

 

Interleukin-10 receptor is a recognised anti-inflammatory target. It is also considered a possible drug target for Crohn's disease and other diseases with serious inflammation - see Drug Discovery Today (2005) 10.2 p93-106.

We expect this query to give average numbers of hits with typical job times.



 
query: 1LQS-Q2
% jobs complete: 100.000
molecules: 39,627,817
hits: 417,344
time: 5:254:12:12:56
Pictures   B C Jones et al Proc Nat Acad Sci (2002) 99 p9404   last updated: 06:08 on 25-AUG-05

Coronavirus proteinase

 

The coronavirus family exhibit one main proteinase sometimes described as '3C-like' because the nature of the catalytic site which fulfils a crucial role in the regulation of the virus life-cycle. The 3-dimensional structure of the SARS main proteinase has not yet been determined experimentally but there is evidence to suggest that it is similar to other coronaviruses. For this project we have selected the structure of a coronavirus which can cause gastroenteritis. The catalytic or active site of this enzyme includes Cysteine and Histidine residues which are considered to be essential for the normal function of the protein. We are seeking small molecule inhibitors which interact with at least one of these residues.



 
query: 1LVO-Q4
% jobs complete: 100.000
molecules: 78,700,430
hits: 1,840
time: 23:221:02:38:36
Pictures   K Anand et al EMBO J (2002) 21 p3213   last updated: 00:07 on 04-APR-04

Integrin a M I domain

 

Integrin a M I domain is also known as Mac-1 is the receptor for MRP14 (see 1irj-q2). This receptor may mediate the membrane inflammaation response. This query targets a different binding site to 1mf7-q2.

Test jobs for this query gave more hits and took longer than typical jobs.



 
query: 1MF7-Q1
% jobs complete: 100.000
molecules: 39,646,323
hits: 543
time: 0:209:01:04:17
Pictures   C J McCleverty and R C Liddington Biochem (2003) 372 p121   last updated: 18:11 on 31-JUL-05

Integrin a M I domain

 

Integrin a M I domain is also known as Mac-1 is the receptor for MRP14 (see 1irj-q2). This receptor may mediate the membrane inflammaation response.

We expect this query to give variable numbers of hits with variable job times.



 
query: 1MF7-Q2
% jobs complete: 100.000
molecules: 39,649,678
hits: 31,025
time: 3:112:04:47:43
Pictures   C J McCleverty and R C Liddington Biochem (2003) 372 p121   last updated: 00:04 on 01-SEP-05

Integrin a M I domain

 

Integrin a M I domain is also known as Mac-1 is the receptor for MRP14 (see 1irj-q2). This receptor may mediate the membrane inflammation response. This query targets uses slightly different search criteria to 1mf7-q1.

Test jobs for this query gave more hits and took longer than typical jobs.



 
query: 1MF7-Q3
% jobs complete: 100.000
molecules: 39,648,942
hits: 73,107
time: 7:319:21:07:23
Pictures   C J McCleverty and R C Liddington Biochem (2003) 372 p121   last updated: 18:08 on 06-SEP-05

7,8-Dihydroneopterin Aldolase

 

7,8-Dihydroneopterin Aldolase (DHNA) has no human equivalent but is an essential enzyme in bacteria including Mycobacterium Tuberculosis, playing a critical role in folate synthesis. This is a novel antibacterial target which is interesting because bacteria in contrast to humans (and other mammals) cannot absorb folate from their environment. Without folate bacteria cannot grow!

This query gives above average number of hits and longer than typical job times.



 
query: 1NBU-Q1
% jobs complete: 100.000
molecules: 39,648,016
hits: 233,931
time: 18:275:19:43:08
Pictures   W J Sanders et al J Med Chem (2004) 47.7 p1709-18   last updated: 06:04 on 01-NOV-05

Phosphodiesterase (Pde4D2)

 

The search for novel PDE4 inhibitors is currently one of the most active fields in the pharmaceutical industry. PDE inhibitors are believed have good potential in the treatment of chronic inflammatory diseases such as asthma as well as rheumatoid arthritis. There are at least four major subtypes of PDE receptor and selectivity may be important in order to reduce side-effects.



 
query: 1OYN-Q1
% jobs complete: 100.000
molecules: 39,874,718
hits: 7,321
time: 4:173:15:38:05
Pictures   R Hersperger J Med Chem (2000) 43 p675-682   last updated: 18:21 on 22-SEP-04

Mycothiol Synthase (MshD)

 

This protein plays an important role in Mycobacterium Tuberculosis and it has been suggested that a molecule which inhibits it may have some drug potential. This is especially the case in drug-resistant forms when inhibit is expected to increase the effectiveness of antimicrobial agents.

We expect this queries to give average numbers of hits. It requires THINK 1.25a or later versions.



 
query: 1OZP-Q1
% jobs complete: 100.000
molecules: 39,627,726
hits: 141,570
time: 5:354:02:26:50
Pictures   M W Vetting et al Protein Science (2003) 12.9 p1954-9   last updated: 12:16 on 04-MAR-05

Coronavirus proteinase

 

The coronavirus family exhibit one main proteinase sometimes described as '3C-like' because the nature of the catalytic site which fulfils a crucial role in the regulation of the virus life-cycle. The 3-D structure of the SARS virus proteinase has been determined by Professor Hilgenfeld at the University of Luebeck who has kindly made this structure available to Find-a-Drug. The catalytic or active site of this enzyme includes Cysteine and Histidine residues which are considered to be essential for the normal function of the protein. As part of the collaboration with Professor Hilgenfeld, the hits from this work will be made available to his group and they will attempt to confirm the binding to the protein site.



 
query: 1P9T-Q3
% jobs complete: 100.000
molecules: 78,706,593
hits: 1,144,581
time: 59:336:20:48:05
Pictures   K Anand, J Ziebuhr, P Wadhwani, J R Mesters R Hilgenfeld Science (2003)   last updated: 00:07 on 03-APR-04

Cystic fibrosis transmembrane conductance regulator (CFTR)

 

Cystic fibrosis transmembrane conductance regulator (CFTR) plays a role in cystic fibrosis. Its Nucleotide-binding domain 1 (NBD1) is often observed with at least one mutation although the biochemical significance of this is not fully understood. This is a speculative query to find molecules which might be therpeutically useful.

We expect this query to give above average numbers of hits with variable job times.



 
query: 1R0X-Q1
% jobs complete: 100.000
molecules: 39,654,773
hits: 188,258
time: 3:302:14:40:16
Pictures   H A Lewis et al, EMBO J (2004) 23.2 p282-93   last updated: 06:07 on 23-AUG-05

Adam33

 

Adam33 is a putative asthma susceptibility gene encoding for a membrane-anchored metalloprotease belonging to the ADAM family. The ADAMs (a disintegrin and metalloprotease) are a family of glycoproteins implicated in cell-cell interactions, cell fusion, and cell signaling. An inhibitor is sought as a potential treatment for Asthma.

We expect these jobs to give more than typical numbers of hits with with some longer than typical job times.



 
query: 1R55-Q1
% jobs complete: 100.000
molecules: 39,656,138
hits: 374,434
time: 9:229:01:32:53
Pictures   P Orth et al J Mol Biol (2004) 335.1 p129-37   last updated: 00:05 on 20-SEP-05

7,8-Dihydroneopterin Aldolase

 

7,8-Dihydroneopterin Aldolase (DHNA) has no human equivalent but is an essential enzyme in bacteria including Mycobacterium Tuberculosis, playing a critical role in folate synthesis. This is a novel antibacterial target which is interesting because bacteria in contrast to humans (and other mammals) cannot absorb folate from their environment. Without folate bacteria cannot grow! This query is based on a different crystal structure to 1nbu-q1.

This query gives above average number of hits and longer than typical job times.



 
query: 1RRI-Q1
% jobs complete: 100.000
molecules: 39,642,848
hits: 139,248
time: 15:062:11:59:32
Pictures   W J Sanders et al J Med Chem (2004) 47.7 p1709-18   last updated: 00:00 on 24-JAN-06

Interleukin-1 beta convertase

 

Interleukin-1 beta convertase (ICE) is also known as Caspase-1 and plays an essential role in the production of Interleukin-1 beta. Suppressing the level of Interleukin-1 beta can reduce inflammation which is especially troublesome in the lungs. It has also been suggested ICE inhibitors may be a useful therapy for Crohn's disease.

We expect this query to give average numbers of hits with typical job times.



 
query: 1RWX-Q1
% jobs complete: 100.000
molecules: 39,627,731
hits: 89,354
time: 9:132:12:43:41
Pictures   T A Rano et al (1997) Chem Biol 4.2 p149-55   last updated: 12:12 on 09-JUN-05

NF-k-b

 

NF-k-b is a transcription factor. It has been suggested that it is a viable anti-inflammatory protein target which may be useful in treating respiratory diseases.

We expect this query to give fewer hits than normal in less time than typical jobs.



 
query: 1SVC-Q1
% jobs complete: 100.000
molecules: 39,649,554
hits: 102,210
time: 6:187:07:36:16
Pictures   C W Muller et al Nature (1995) 373 p311-7   last updated: 00:12 on 15-SEP-05

Sulfotransferase

 

This enzyme is responsible for a step in the synthesis of trehalose-2-sulfase (T2L) which is a key component of sulfolipid-1 (SL1) In mycobacterium tuberculosis (the bacterium which causes TB), inhibiting this enzyme stops T2L being made with the consequence that SL1 is no longer formed. A sulfotransferase inhibitor might be a novel therapy for TB.

This query gave above average number of hits and slightly longer than typical job times.



 
query: 1TEX-Q1
% jobs complete: 100.000
molecules: 39,627,539
hits: 704,587
time: 12:137:11:29:55
Pictures   J D Mougous et al Nat Struct Mol Biol (2004) 11.8 p686-7   last updated: 18:20 on 02-MAR-05

Thymidylate kinase (TMPK)

 

This kinase converts thymidine monophosphate (TMP) to the di- and tri-phosphates. Inhibiting this process would be expected to significantly disrupt the cell cycle (ie growth). There is sufficient variation from the mammalian form and that found in mycobacterium tuberculosis to give scope for selective inhibition. This query is based a different crystal structure to 1g3u-q1.

In test jobs, this query took less time than typical jobs and gave below average numbers of hits.



 
query: 1W2G-Q1
% jobs complete: 100.000
molecules: 39,652,331
hits: 85,448
time: 6:197:08:45:03
Pictures   I Li de la Sierra et al J Mol Biol (2001) 311 p87-100   last updated: 18:03 on 22-DEC-05