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May 3 - 4, 2005 Meeting Agenda

April 29, 2005

 

FIFRA SCIENTIFIC ADVISORY PANEL (SAP)

OPEN MEETING

MAY 3-4, 2005

FIFRA SAP WEB SITE http://www.epa.gov/scipoly/sap/

OPP Docket Telephone: (703) 305-5805

Docket Number: OPP-2005-0060

 

TSCA INVENTORY NOMENCLATURE FOR ENZYMES AND PROTEINS

 

TUESDAY, MAY 3, 2005

Holiday Inn – Rosslyn at Key Bridge

1900 North Fort Myer Drive
Arlington , Virginia 22209
Telephone: (703) 807-2000

8:30 AM Introduction and Identification of Panel Members – Steven Heeringa, Ph.D., FIFRA SAP Session Chair

8:45 AM Administrative Procedures by Designated Federal Official – Paul Lewis, Ph.D.

8:50 AM Welcome – Clifford Gabriel, Ph.D., Director, Office of Science Coordination and Policy, EPA

8:55 AM Opening Remarks – Mr. Charles Auer, Director, Office of Pollution Prevention and Toxics, EPA

9:00 AM Introduction – Mr. Neil Patel, Associate Director, Economics, Environment and Technology Division, Office of Pollution Prevention and Toxics, EPA

9:10 AM Background on TSCA Inventory – Greg Fritz, Ph.D., Chemist, Economics, Environment and Technology Division, Office of Pollution Prevention and Toxics, EPA

9:40 AM Agency’s Proposed Approach for Enzyme Identification on the TSCA Inventory - Mark Segal, Ph.D., Senior Microbiologist, Risk Assessment Division, Office of Pollution Prevention and Toxics, EPA

10:20 AM BREAK

10:30 AM Public Comments

 

EPA is proposing the use of four data elements (function, sequence, source, and processing) for comprehensively listing and distinguishing among enzymes on the TSCA Inventory. The following questions are intended to help the Agency make a final decision on how enzymes will be listed on the Inventory in the future.

Function

The function of an enzyme refers to its catalytic activity. Internationally-accepted nomenclature conventions of the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) describe and categorize enzymes based on their function. The NC-IUBMB assigns enzymes an Enzyme Committee (EC) code number based on the specific reaction(s) catalyzed by the enzyme, the nature of the bond involved, and the substrate acted upon. EPA intends to incorporate function into TSCA Inventory enzyme listings by using these EC codes and the systematic name for the specific catalytic activity. In the questions below, please identify the scientific merit for using function information to differentiate among enzymes and identify what level of detail regarding function would be scientifically appropriate for this purpose.

1.While the Agency recognizes the practical, historical advantages of using function to describe enzymes, in the context of the Agency’s need for unique and unambiguous naming, what is the scientific rationale for identifying an enzyme based on the chemical reaction(s) it catalyzes?

2. How precise is the IUBMB EC categorizing system for describing enzyme function? For example, in addition to the EC function category to which an enzyme belongs, what additional information about enzyme structure and/or chemical properties, if any, would be gained by a more detailed functional description that included

3. The Agency is trying to gauge the probable comprehensiveness of enzyme catalytic function descriptions for subsequent enzyme reporting.

a. How common are multifunctional enzymes?

b. How frequently are new catalytic functions for existing enzymes discovered?

c. How good are existing models to assess the likelihood that an enzyme may have several catalytic functions?

 

12:30 PM LUNCH

1:30 PM Panel Discussion

Sequence The amino acid sequence of an enzyme is known as its primary structure. It is a systematic representation of the linear sequence of amino acids that are connected via amide bonds to form a polypeptide. In the questions below, please consider what scientific support there is for using sequence information to differentiate among enzymes and what level of detail would be scientifically appropriate for this purpose.

4. What information about an enzyme could be gained by identifying it based on its amino acid sequence?

5. The Agency is trying to assess the expected amount of variation in an enzyme amino acid sequence due to various causes in spite of current quality control standards.

a. How much and what type of variation (including substitutions, deletions, and additions) can be expected in the amino acid sequence of an enzyme produced in multiple batches that will arise due to unintended differences in production conditions? Estimate a percentage, number of residues, or other quantifiable measure of variation.

b. How much and what type of variation (including substitutions, deletions, and additions) can be expected in the amino acid sequence of an enzyme within a given sample of a single production batch due to individual-level variation in an enzyme-producing population? Estimate a percentage, number of residues, or other quantifiable measure of variation.

c. How much and what type of variation (including substitutions, deletions, and additions) can be expected in the amino acid sequence of an enzyme across multiple samples collected over time (e.g., in microbial cultures stored for extended periods) due to changes in an enzyme-producing population? Estimate a percentage, number of residues, or other quantifiable measure of variation.

 

i..Over what time scale will such variation arise? That is, is there a predictable relationship between the amount of variation and the length of time in culture?

ii. What kinds of changes might occur to an enzyme preparation if naturally occurring variants become the dominant component (e.g., changes in rates of activity, reactions catalyzed, substrate range, response to environmental conditions)?

iii.Have any enzymes in commerce or research been known to change in amino acid sequence over time? Have any been known to remain unchanged in amino acid sequence for a year/decade or longer? 

d. How important are deletions and/or excisions in determining differences between enzymes?

 

3:00 PM BREAK

3:15 PM Panel Discussion (continued)

 

 

4 :30 PMADJOURNMENT


FIFRA SCIENTIFIC ADVISORY PANEL (SAP)

OPEN MEETING

MAY 4, 2005

FIFRA SAP WEB SITE http://www.epa.gov/scipoly/sap/

OPP Docket Telephone: (703) 305-5805

Docket Number: OPP-2005-0060

 

TSCA INVENTORY NOMENCLATURE FOR ENZYMES AND PROTEINS

 

WEDNESDAY, MAY 4, 2005

Holiday Inn – Rosslyn at Key Bridge

1900 North Fort Myer Drive
Arlington , Virginia 22209
Telephone: (703) 807-2000

8:30 AM Introduction and Identification of Panel Members – Steven Heeringa, Ph.D., FIFRA SAP Session Chair

8:35 AM Administrative procedures by Designated Federal Official – Paul Lewis, Ph.D.

8:40 AM Follow-up from Previous Day’s Discussion - Mark Segal, Ph.D., Senior Microbiologist, Risk Assessment Division, Office of Pollution Prevention and Toxics, EPA

9:00 AM Panel Discussion (continued)

 Source The source of an enzyme refers to (1) the organism from which the gene encoding the enzyme was derived, i.e., the original source and(2) the organism or manufacturing platform (e.g., tissue culture) in which the enzyme is produced, i.e., the production source. In the questions below, please consider what scientific support there is for using source information to differentiate among enzymes and what level of detail would be scientifically appropriate for this purpose.   What information about an enzyme’s structure could be gained by knowing the original source of the enzyme? the production source of the enzyme? If original source information were used as an identification element to discriminate among enzymes, what level of taxonomic specificity (e.g., family, genus, species, subspecies, population, biovar, culture line) would be most scientifically appropriate to use for each of the following categories? What if production source information were used? (Note: EPA recognizes that taxonomic revisions may change the names of particular organisms and can utilize mechanisms for normalizing organism nomenclature, but that consideration does not need to be addressed by the panel.)

10:30 AM BREAK

d. manipulations of an enzymes production source prior to and/or following gene transfer?

e. other relevant aspects of source that are not mentioned (please specify what would be of value).

12:00 PM LUNCH

1 :00 PM Panel Discussion (continued)

13 . What information about an enzyme’s structure could be gained by knowing which of certain processing techniques were used in its production?

14. EPA anticipates that certain processing techniques may be so routine and/or chemically inconsequential that their reporting would be unnecessary, while other processing techniques would have significant effects on the chemical structure and/or properties of an enzyme. The Agency is trying to assess how practical it would be to create a list of processing techniques that need not be included as part of enzyme identity.

3:00 AM BREAK

3 :15 PM Panel Discussion (continued)

 

 

5 :00 PMADJOURNMENT

 

Please be advised that agenda times are approximate. For further information, please contact the Designated Federal Official for this meeting, Paul Lewis via telephone: (202) 564-8450; fax: (202) 564-8382; or email: lewis.paul@epa.gov


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